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Choi W, Lauwers GY, Slavik T. Inflammatory disorders of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:135-194. [DOI: 10.1002/9781119423195.ch11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Giammanco A, Anzalone R, Serra N, Graceffa G, Vieni S, Scibetta N, Rea T, Capra G, Fasciana T. Helicobacter pylori and Epstein-Barr Virus Co-Infection in Gastric Disease: What Is the Correlation with p53 Mutation, Genes Methylation and Microsatellite Instability in a Cohort of Sicilian Population? Int J Mol Sci 2023; 24:ijms24098104. [PMID: 37175810 PMCID: PMC10179236 DOI: 10.3390/ijms24098104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/06/2023] [Accepted: 04/10/2023] [Indexed: 05/15/2023] Open
Abstract
Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with and without gastric diseases. The patients were stratified into four groups. Significant methylation status differences among CDH1, DAPK, COX2, hMLH1 and CDKN2A were observed for coinfected (Hp-EBV group) patients; particularly, a significant presence of COX2 (p = 0.0179) was observed. For microsatellite instability, minor stability was described in the Hp-HBV group (69.23%, p = 0.0456). Finally, for p53 mutation in the EBV group, exon 6 was, significantly, most frequent in comparison to others (p = 0.0124), and in the Hp-EBV group exon 8 was, significantly, most frequent in comparison to others (p < 0.0001). A significant positive relationship was found between patients with infection (Hp, EBV or both) and p53 mutation (rho = 0.383, p = 0.0001), methylation status (rho = 0.432, p < 0.0001) and microsatellite instability (rho = 0.285, p = 0.004). Finally, we observed among infection and methylation status, microsatellite instability, and p53 mutation a significant positive relationship only between infection and methylation status (OR = 3.78, p = 0.0075) and infection and p53 mutation (OR = 6.21, p = 0.0082). According to our analysis, gastric disease in the Sicilian population has different pathways depending on the presence of various factors, including infectious agents such as Hp and EBV and genetic factors of the subject.
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Affiliation(s)
- Anna Giammanco
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
| | - Rita Anzalone
- Department of Surgical Oncological and Oral Sciences, University of Palermo, 90133 Palermo, Italy
| | - Nicola Serra
- Department of Public Health, University Federico II of Naples, 80138 Napoli, Italy
| | - Giuseppa Graceffa
- Department of Surgical Oncological and Oral Sciences, University of Palermo, 90133 Palermo, Italy
| | - Salvatore Vieni
- Department of Surgical Oncological and Oral Sciences, University of Palermo, 90133 Palermo, Italy
| | - Nunzia Scibetta
- Anatomopathology Unit, Arnas Civico Di Cristina Benfratelli Hospital, 90127 Palermo, Italy
| | - Teresa Rea
- Public Health Department, Federico II University Hospital, 80131 Naples, Italy
| | - Giuseppina Capra
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
| | - Teresa Fasciana
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
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Lei Y, Liu C, Wan X, Yang Y, Yao Y, Luo L, Huang T, Li J. Polymyositis as a paraneoplastic syndrome of a patient with primary pulmonary lymphoepithelioma-like carcinoma: a case report and literature review. J Cardiothorac Surg 2022; 17:120. [PMID: 35581657 PMCID: PMC9113618 DOI: 10.1186/s13019-022-01860-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 04/24/2022] [Indexed: 11/29/2022] Open
Abstract
Background Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer, which mostly occurred in non-smoking Asian populations. The prognosis of this tumor is better than other lung cancers. Polymyositis, a kind of idiopathic inflammatory myopathies, may negatively affect the prognosis of patients with lung cancer as a paraneoplastic syndrome (PNPS). LELC is seldomly accompanied by PNPS, thus the treatment strategy and prognosis should be discussed. Case presentation We report a 49-year-old female patient who was hospitalized for “symmetric limb weakness and pain for more than 2 months”. Glucocorticoid-based anti-inflammatory therapy had been performed for over 3 weeks before the patient was hospitalized, however, in vain. The result of serum autoimmune antibody showed Anti-nRNP/Sm ( +). The serum level of myoglobin, lactate dehydrogenase and creatine kinase elevated significantly. An electromyogram revealed peripheral nerves injury and myogenic damages. Imaging showed a mass in the posterior basal segment of the left lung. A percutaneous transthoracic needle biopsy was performed and the pathological result was LELC. The patient was diagnosed with pulmonary LELC accompanied by polymyositis. Positron emission tomography-computed tomography (PET-CT) showed only ipsilateral hilar and mediastinal lymph nodes metastasis. Video-assisted thoracoscopic left lower lobectomy and systematic mediastinal lymphadenectomy were performed. The postoperative pathological stage was T2N2M0, IIIA (UICC 8th), and the patient received adjuvant chemotherapy and subsequent radiotherapy. The patient was followed up for 5 months with no recurrence of tumor and the limb weakness and pain were relieved apparently after the successful comprehensive treatment of her primary tumor. Conclusion Pulmonary LELC is a rare subtype of non-small cell lung cancer seldomly accompanied by PNPS. Though polymyositis is associated with lung cancer, it is easy to ignore this relationship when a patient is diagnosed with LELC in the clinic. Surgery based comprehensive treatment of primary tumor can lead to a prospective prognosis in pulmonary LELC patients with PNPS. And successful treatment of pulmonary LELC can also improve symptoms of PNPS.
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Affiliation(s)
- Yu Lei
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China
| | - Caiyang Liu
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China
| | - Xiu Wan
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China
| | - Yanhui Yang
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China
| | - Yi Yao
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China
| | - Lei Luo
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China
| | - Tingyu Huang
- Department of Pathology, The First People's Hospital of Neijiang, Neijiang, 641000, Sichuan, China
| | - Ji Li
- Department of Cardiothoracic Surgery, The First People's Hospital of Neijiang, Shizhong District, No. 1866, West Section of Hanan Avenue, Neijiang, 641000, Sichuan, China.
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Primary lymphoepithelioma-like carcinoma of the esophagus with metastatic lymph node and gastric cancer. Clin J Gastroenterol 2021; 14:1329-1336. [PMID: 34328628 DOI: 10.1007/s12328-021-01489-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 07/24/2021] [Indexed: 10/20/2022]
Abstract
Upper gastrointestinal lymphoepithelioma-like carcinoma (LELC) is a rare disease-especially esophageal LELC (ELELC). Here, we report a surgically treated case of ELELC with gastric carcinoma. The patient was a 68-year-old asymptomatic Japanese man. Endoscopy revealed a submucosal-like protruding tumor located in the anterior wall of the esophagus 31-33 cm from the upper incisors and a slightly ulcerative lesion at the antrum of stomach. Histopathological diagnosis from biopsy of the esophageal lesion revealed a poorly differentiated squamous cell carcinoma; the stomach lesion was found to be well-differentiated tubular adenocarcinoma. CT showed a swollen lymph node along the left recurrent nerve. On the basis of a diagnosis of esophageal and gastric cancer, we performed esophagectomy with three-field lymph node dissection and partial gastrectomy. Histopathology of the resected esophageal tumor revealed solid nests of cancer cells, with substantial infiltration of lymphoid cells into the stroma. There were poorly differentiated cancer cells with large nuclei in the lymph node. In situ hybridization for Epstein-Barr virus showed no nuclear signal in the tumor cells. Immunohistochemistry gave a diagnosis of ELELC.
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Clauditz TS, Wallace MB, Lauwers GY. Inflammatory Disorders of the Stomach. GASTROINTESTINAL PATHOLOGY 2021:73-98. [DOI: 10.1002/9781119073048.ch4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Guo C, Wei J, Scott RS, Chen Y, Chen Z, Zhao W, Zhang C, Wang B, Chai C, Dai G, Li M, Zhang F. Prevalence and characteristics of Epstein‐Barr virus associated gastric carcinoma in Gansu Province, Northwest China with mRNA expression of glycoprotein BMRF2. J Med Virol 2019; 92:356-363. [DOI: 10.1002/jmv.25616] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 10/24/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Chen Guo
- School of Basic Medical SciencesLanzhou UniversityLanzhou Gansu China
- First Affiliated Clinical HospitalLanzhou UniversityLanzhou Gansu China
| | - Jing Wei
- School of Basic Medical SciencesLanzhou UniversityLanzhou Gansu China
| | - Rona S. Scott
- Center for Molecular and Tumor VirologyLouisiana State University Health Sciences CenterShreveport Louisiana
- Department of Microbiology and ImmunologyLouisiana State University Health Sciences CenterShreveport Louisiana
- Feist‐Weiller Cancer CenterLouisiana State University Health Sciences CenterShreveport Louisiana
| | - Yonglin Chen
- First Affiliated Clinical HospitalLanzhou UniversityLanzhou Gansu China
| | - Zhifeng Chen
- Department of Otolaryngology‐Head and Neck SurgeryThe 940th Hospital of Joint Logistics Support Force of CPLALanzhou Gansu China
| | - Wenjie Zhao
- School of Basic Medical SciencesLanzhou UniversityLanzhou Gansu China
| | - Chenli Zhang
- School of Basic Medical SciencesLanzhou UniversityLanzhou Gansu China
| | - Binsheng Wang
- First Affiliated Clinical HospitalLanzhou UniversityLanzhou Gansu China
| | - Chen Chai
- First Affiliated Clinical HospitalLanzhou UniversityLanzhou Gansu China
| | - Gan Dai
- Xiangya School of MedicineCentral South UniversityChangsha Hunan China
| | - Min Li
- School of Basic Medical SciencesLanzhou UniversityLanzhou Gansu China
| | - Fangfang Zhang
- School of Basic Medical SciencesLanzhou UniversityLanzhou Gansu China
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Xuan H, Zhengjun C, Yang H, Guohan C. Case report: mutation analysis of primary pulmonary lymphoepithelioma-like carcinoma via whole-exome sequencing. Diagn Pathol 2019; 14:67. [PMID: 31248429 PMCID: PMC6598353 DOI: 10.1186/s13000-019-0811-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 04/11/2019] [Indexed: 11/10/2022] Open
Abstract
Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumor subtype accounting for around 0.9% of lung cancers. At present, research on LELC mainly focuses on pathological diagnosis, while the molecular mutation landscape is still unclear. Case presentation A 72-year-old female presented a productive cough for three weeks followed by severe symptoms for another week. Respiratory sounds were weak and coarser in the right lung field. F-FDG PET-CTA showed a hypermetabolic mass in the upper lobe of the right lung as well as the enlargement of right hilar and subcarinal lymph nodes. Hematoxylin-eosin staining and immunohistochemistry staining of the biopsy established the diagnosis of primary pulmonary LELC. After thoracoscopic-assisted radical resection of right lung cancer and middle lobe of right lung, the patient’s vital signs were stable without apparent productive cough, chest pain, chest tightness and other subjective discomforts. Furtherwhole exome sequencing of the patient’s tumor tissue and leukocytes (served as a germline mutation control) revealed 613 somatic gene mutations, and of which mutations in PRIM2, KCNB1, CDH1, and ATRX were most likely related to the LELC pathogenesis. The recurrence of gene mutations from various cancers database and a tumor mutation burden (TMB) of 18.7 mutations/mb were revealed as well. Conclusion Our findings have illustrated the genomic profile of a primary pulmonary LELC case and provided a positive biomarker that immune checkpoint blockade is potentially effective for this patient in further treatment.
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Affiliation(s)
- Hong Xuan
- Department of Thoracic, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Chai Zhengjun
- Department of Thoracic, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Han Yang
- Department of Pathology, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Chen Guohan
- Department of Thoracic, Shanghai East Hospital, Tongji University, Shanghai, China.
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Kılıç Bağır E, Açıkalın A, Ergin M, Sezgin G, Küpeli S, Seydaoğlu G. Pediatrik lenfomalarda histopatolojik subtip ve Ebstein-Barr virus ilişkisi: immünohistokimyasal ve in situ hibridizasyon çalışması. CUKUROVA MEDICAL JOURNAL 2018. [DOI: 10.17826/cumj.368637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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Epstein-Barr virus-induced up-regulation of TCAB1 is involved in the DNA damage response in nasopharyngeal carcinoma. Sci Rep 2017; 7:3218. [PMID: 28607398 PMCID: PMC5468285 DOI: 10.1038/s41598-017-03156-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 04/25/2017] [Indexed: 02/05/2023] Open
Abstract
Telomerase Cajal body protein 1 (TCAB1), which is involved in Cajal body maintenance, telomere elongation and ribonucleoprotein biogenesis, has been linked to cancer predisposition, including nasopharyngeal carcinoma (NPC), due to its oncogenic properties. However, there are no specific reports to date on the functional relevance of TCAB1 and Epstein–Barr virus (EBV), which is considered to be a risk factor for NPC. In this study, we first examined NPC clinical tissues and found a notable overexpression of TCAB1 in EBV-positive specimens. Secondly, on a cellular level, we also observed that TCAB1 expression rose gradually along with the increased duration of EBV exposure in NPC cell lines. Additionally, EBV infection promoted cell proliferation and telomerase activity, but the activation was significantly inhibited after TCAB1 knockdown. Moreover, depletion of TCAB1 caused both cell cycle arrest and apoptosis, and suppressed the activation of ataxia telangiectasia and Rad3 related protein (ATR) induced by EBV, resulting in accumulation of DNA damage. Taken together, we here demonstrate that up-regulated expression of TCAB1, induced by EBV in the development of NPC, is involved in stimulating telomerase activity and regulating the DNA damage response within the context of EBV infection.
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Raudenska M, Gumulec J, Fribley AM, Masarik M. HNSCC Biomarkers Derived from Key Processes of Cancerogenesis. TARGETING ORAL CANCER 2016:115-160. [DOI: 10.1007/978-3-319-27647-2_7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Yamamoto Y, Fujisaki J, Omae M, Hirasawa T, Igarashi M. Helicobacter pylori-negative gastric cancer: characteristics and endoscopic findings. Dig Endosc 2015; 27:551-61. [PMID: 25807972 DOI: 10.1111/den.12471] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 03/09/2015] [Accepted: 03/12/2015] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori (H. pylori) leads to chronic gastritis and eventually causes gastric cancer. The prevalence of H. pylori infection is gradually decreasing with improvement of living conditions and eradication therapy. However, some reports have described cases of H. pylori-negative gastric cancers (HpNGC), and the prevalence was 0.42-5.4% of all gastric cancers. Diagnostic criteria of HpNGC vary among the different reports; thus, they have not yet been definitively established. We recommend negative findings in two or more methods that include endoscopic or pathological findings or serum pepsinogen test, and negative urease breath test or serum immunoglobulin G test and no eradication history the minimum criteria for diagnosis of HpNGC. The etiology of gastric cancers, excluding H. pylori infection, is known to be associated with several factors including lifestyle, viral infection, autoimmune disorder and germline mutations, but the main causal factor of HpNGC is still unclear. Regarding the characteristics of HpNGC, the undifferentiated type (UD-type) is more frequent than the differentiated type (D-type). The UD-type is mainly signet ring-cell carcinoma that presents as a discolored lesion in the lower or middle part of the stomach in relatively young patients. The gross type is flat or depressed. The D-type is mainly gastric adenocarcinoma of the fundic gland type that presents as a submucosal tumor-like or flat or depressed lesion in the middle and upper part of the stomach in relatively older patients. Early detection of HpNGC enables minimally invasive treatment which preserves the patient's quality of life. Endoscopists should fully understand the characteristics and endoscopic findings of HpNGC.
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Affiliation(s)
- Yorimasa Yamamoto
- Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan
| | - Junko Fujisaki
- Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan
| | - Masami Omae
- Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan
| | - Toshiaki Hirasawa
- Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan
| | - Masahiro Igarashi
- Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan
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Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms. Gastric Cancer 2015; 18:246-55. [PMID: 24771002 DOI: 10.1007/s10120-014-0376-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 03/28/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric lymphoepithelioma-like carcinoma (LELC) is a rare entity that is closely associated with Epstein-Barr virus (EBV). However, the EBV latency pattern and genome polymorphisms in gastric LELC have not been systematically explored. METHODS The clinicopathological features, EBV latency pattern and genome polymorphisms of EBV-positive gastric LELC in Guangzhou, southern China were investigated and compared with those of ordinary EBV-associated gastric carcinoma (EBVaGC) in the same area. RESULTS Ten (1.42%) of 702 gastric carcinoma cases were identified as gastric LELC, in which eight (80%) cases were EBV-positive. The clinicopathological characteristics and EBV latency pattern of EBV-positive gastric LELC were similar to those of ordinary EBVaGC. In EBV genotype analysis, type A strain, type F, I, mut-W1/I, XhoI- and del-LMP1 variants were predominant among EBV-positive gastric LELCs, accounting for eight (100%), six (75%), eight (100%), seven (87.5%), five (62.5%) and six (75%) cases, respectively, which are similar to those in ordinary EBVaGC. For EBNA1 polymorphisms, the V-leu and P-ala subtypes were predominant in EBV-positive gastric LELC, which is different from the predominant V-val subtype in ordinary EBVaGC. EBV-positive gastric LELC has a favorable prognosis when compared to ordinary EBVaGC (median survival time 43.0 vs. 18.0 months). CONCLUSIONS Gastric LELC is strongly associated with EBV and EBV-positive gastric LELC should be regarded as a special subtype of EBVaGC. This, to our best knowledge, is the first time in the world that the EBV latency pattern and genome polymorphisms of EBV-positive gastric LELC are systematically revealed.
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Yasuda Y, Tobino K, Ko Y, Asaji M, Yamaji Y, Tsuruno K, Miyajima H, Mukasa Y, Ebi N. Successful treatment with carboplatin and pemetrexed for multiple lymph node metastases of lymphoepithelioma-like carcinoma from an unknown primary site. Intern Med 2015; 54:2651-4. [PMID: 26466705 DOI: 10.2169/internalmedicine.54.5020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We herein report the case of an 80-year-old Japanese man with multiple lymph node metastases of lymphoepithelioma-like carcinoma (LELC) from an unknown primary site. The patient was admitted to our hospital due to hoarseness and left supraclavicular lymphadenopathy. Contrast-enhanced whole-body computed tomography revealed mediastinal, left supraclavicular, and left axillary lymphadenopathy. A left supraclavicular lymph node biopsy was performed and the specimen was consequently diagnosed as exhibting LELC. The patient's Eastern Cooperative Oncology Group performance status was 0, therefore he was started on chemotherapy with carboplatin and pemetrexed. His lymph nodes responded well to four cycles of chemotherapy without any intolerable adverse effect.
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Polanska H, Raudenska M, Gumulec J, Sztalmachova M, Adam V, Kizek R, Masarik M. Clinical significance of head and neck squamous cell cancer biomarkers. Oral Oncol 2014; 50:168-77. [PMID: 24382422 DOI: 10.1016/j.oraloncology.2013.12.008] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 12/09/2013] [Accepted: 12/11/2013] [Indexed: 10/25/2022]
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Cytotoxic T cell adoptive immunotherapy as a treatment for nasopharyngeal carcinoma. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2013; 21:256-9. [PMID: 24351754 DOI: 10.1128/cvi.00121-13] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress.
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Ambrosio MR, Mastrogiulio MG, Barone A, Rocca BJ, Gallo C, Lazzi S, Leoncini L, Bellan C. Lymphoepithelial-like carcinoma of the parotid gland: a case report and a brief review of the western literature. Diagn Pathol 2013; 8:115. [PMID: 23856064 PMCID: PMC3751049 DOI: 10.1186/1746-1596-8-115] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2013] [Accepted: 06/25/2013] [Indexed: 01/14/2023] Open
Abstract
Background Primary lymphoepithelial-like carcinoma of the parotid gland is a rare tumour with an increased incidence among Eskimos and Orientals. In these populations, it is usually associated with Epstein-Barr virus. In Western countries, salivary gland lymphoepithelial-like carcinomas are uncommon and only 14 cases have been described so far; among these, only five cases showed Epstein-Barr virus positivity. Case report A 45-year-old woman was admitted to Siena Hospital for evaluation of a pre-existent (2 years) painless and tender submandibular mass, rapidly enlarging since two months. On physical examination, a 2.5-cm mass was found in the right parotid. It was firm, mobile and non-tender. Laboratory data were within reference range. Nuclear magnetic resonance detected a 2,5×1,5×1-cm well-circumscribed mass in the deep lobe of the right parotid. A total right paroditectomy with dissection of a satellite lymph node was performed. On the basis of morphological, immunohistochemical and molecular biology findings, a diagnosis of stage II (according to TNM7) Epstein Barr-virus positive, undifferentiated lymphoepithelial-like carcinoma of the parotid gland was made. Twenty months after surgery the patient was free of disease. Conclusions Further studies seem to be necessary to completely elucidate the oncogenic role of Epstein Barr-virus in these tumors, which have identical morphology but different prognosis and variable presence of the virus. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1260381551000616
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Abstract
Post-transplant hemopathies are a serious complication of organ transplantation. They include several entities: non-hodgkin lymphoma, Hodgkin disease and myeloma. The pathophysiology, clinical and histological features, treatment and evolution of these diseases are different, but share some similarities. Among factors involved in lymphomagenesis, the role of Epstein Barr virus and immunosuppression are central. EBV primo-infection or reactivation together with a deep depression of T-cell immunity is at particular risk of lymphoma development. The clinical expression and outcome of lymphomas are varied. Assays for EBV replication quantification have been developed leading to immunosuppression decreasing and antiviral therapy when the replication increases. Treatment of post-transplant lymphoproliferations consists mainly in immunotherapy and chemotherapy. Hodgkin disease and myeloma are rare after transplantation; their management is close to the one of immunocompetent patients. The recurrence of myeloma, amyloidosis or light chain deposition disease seems frequent after transplantation and only patients with disappearance of monoclonal component should be proposed for transplantation. On the opposite, the risk of recurrence appears lower for Hodgkin disease; therefore the transplantation of patients with a history of Hodgkin disease looks possible.
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Hayashi T, Haba R, Tanizawa J, Katsuki N, Kadota K, Miyai Y, Bando K, Shibuya S, Nakano M, Kushida Y. Cytopathologic features and differential diagnostic considerations of primary lymphoepithelioma-like carcinoma of the lung. Diagn Cytopathol 2011; 40:820-5. [PMID: 21433005 DOI: 10.1002/dc.21670] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Accepted: 01/22/2011] [Indexed: 11/11/2022]
Abstract
Primary lymphoepithelioma-like carcinoma (LELC) of the lung is an extremely rare disease that occurs more commonly in Asians, and is composed of undifferentiated carcinoma with prominent lymphoid stroma. LELC is reported to be closely associated with Epstein-Barr virus (EBV) infection. A case is presented here in which bronchial brushing smears in a 70-year-old man, revealed large clusters of neoplastic cells with scant cytoplasm. The nuclei were large, hyperchromatic, of irregular contour and with prominent nucleoli. Also identified were prominent intratumoral lymphoid infiltration and brisk mitotic figures. We detected EBV-coded small RNA in situ hybridization in smears. A cytologic diagnosis of a LELC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Cords or nests of large neoplastic cells with enlarged nuclei and prominent nucleoli with marked lymphoid infiltration and lymphoid stroma were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK5/6, CK34βE12, Napsin A and Bcl-2 but were negative for CK7, CK14, CK20, EMA, TTF-1, chromogranin A, synaptophysin and CD56. The proliferative index with MIB-1 was around 60%, and the p53 positive cells around 20%. The diagnosis of primary LELC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical and EBER results, and a detailed systemic examination to exclude possible extrapulmonary (nasopharyngeal) origin. We report the cytopathological features of LELC of the lung and demonstrate here for the first time the positivity of the EBER with RNA-ISH method in smears with emphasis on differential diagnostic considerations.
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Affiliation(s)
- Toshitetsu Hayashi
- Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa Prefecture, Japan.
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Peripheral T-cell Lymphoma With Progression to a Clonally Related, Epstein Barr Virus+, Cytotoxic Aggressive T-cell Lymphoma: Evidence for Secondary EBV Infection of an Established Malignant T-cell Clone. Am J Surg Pathol 2010; 34:1382-7. [DOI: 10.1097/pas.0b013e3181ec577a] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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21
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Novel approach to the formulation of an Epstein-Barr virus antigen-based nasopharyngeal carcinoma vaccine. J Virol 2010; 84:407-17. [PMID: 19846527 DOI: 10.1128/jvi.01303-09] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.
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Hisamatsu A, Nagai T, Okawara H, Nakashima H, Tasaki T, Nakagawa Y, Hashinaga M, Kai S, Yokoyama S, Murakami K, Fujioka T. Gastritis associated with Epstein-Barr virus infection. Intern Med 2010; 49:2101-5. [PMID: 20930436 DOI: 10.2169/internalmedicine.49.3789] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Infectious mononucleosis is a self-limiting clinical syndrome caused by primary Epstein-Barr virus (EBV) infection. EBV-associated gastritis, however, has rarely been documented. We report a case of a 17-year-old woman who presented with fever, sore throat, and epigastric pain. Upper endoscopy revealed diffuse granular mucosae and elevated lesions in the stomach. Histologically, the biopsied mucosa was infiltrated by numerous atypical lymphocytes. From clinical, histopathologic, immunohistochemical, and in situ hybridization analyses, we diagnosed EBV-associated gastritis. Her symptoms spontaneously resolved, and follow-up endoscopy revealed improvement and no atypical lymphocytes. To prevent misdiagnosis and unnecessary treatment, the possibility of EBV-associated gastritis should be considered.
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Affiliation(s)
- Akari Hisamatsu
- Department of Gastroenterology, Oita Kouseiren Tsurumi Hospital, Beppu.
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Tiwawech D, Srivatanakul P, Karalak A, Ishida T. Association between EBNA2 and LMP1 subtypes of Epstein-Barr virus and nasopharyngeal carcinoma in Thais. J Clin Virol 2008; 42:1-6. [DOI: 10.1016/j.jcv.2007.11.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2007] [Revised: 10/17/2007] [Accepted: 11/11/2007] [Indexed: 11/28/2022]
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Takashima K, Ohashi M, Kitamura Y, Ando K, Nagashima K, Sugihara H, Okuno K, Sairenji T, Hayashi K. A new animal model for primary and persistent Epstein-Barr virus infection: human EBV-infected rabbit characteristics determined using sequential imaging and pathological analysis. J Med Virol 2008; 80:455-66. [PMID: 18205213 DOI: 10.1002/jmv.21102] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Most adults have persistent Epstein-Barr virus (EBV)-infection. Adolescents and young adults with primary EBV-infection frequently develop infectious mononucleosis. Latent EBV-infection is associated with various diseases, neoplasms, and hematological disorders. In vivo animal models of human EBV infection, such as non-human primates, have had limited success. A new rabbit model for primary human EBV-infection is described in this study. Seven male rabbits inoculated intravenously with EBV were sequentially imaged by ultrasonography and computed tomography, and examined for anti-EBV-VCA titer and EBV-DNA levels in blood. Six rabbits demonstrated transient splenomegaly, increased anti-EBV-VCA titers and/or EBV-DNA in blood. Transient infiltration of some EBER1-positive lymphocytes was observed in biopsied liver tissues. After splenomegaly, two rabbits tested continuously negative, two alternatively positive and negative, and one consistently positive EBV detection in blood for 470 days. One tested negative for both EBV DNA and splenomegaly. On the 14th day, mild to moderate numbers of EBER1-positive lymphocytes expressing LMP1, EBNA2, or ZEBRA infiltrated mainly in enlarged white pulps of two splenectomized materials. These cells included both B and T cells. EBV clonality analysis revealed an oligoclonal pattern. These indicate that EBV-inoculated rabbits exhibiting heterogenous host reactions are a good model for primary and persistent human EBV infection.
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Affiliation(s)
- Kazuaki Takashima
- Division of Molecular Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan
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Ikegaya H, Motani H, Sakurada K, Sato K, Akutsu T, Yoshino M. Forensic application of Epstein-Barr virus genotype: Correlation between viral genotype and geographical area. J Virol Methods 2008; 147:78-85. [PMID: 17868913 DOI: 10.1016/j.jviromet.2007.08.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2007] [Revised: 08/02/2007] [Accepted: 08/02/2007] [Indexed: 01/01/2023]
Abstract
Using 50 forensic blood samples, the latent membrane protein 2A (LMP-2A) gene of Epstein-Barr virus (EBV) DNA was amplified to find a geographic correlation among the EBV genotypes. EBV DNA was detected in nine samples. From a phylogenetic analysis using 18 reported sequences as a reference, six EBV subtypes (Ia, Ib, Ic IIa, IIb, and IIc) were found. Japanese isolates were included in subtypes Ia or IIa. All the Asian reference isolates, except isolate D6, were included in subtype Ia or IIa. Mediterranean, an Alaskan and other African isolates were included in types Ib, Ic, IIb and IIc. The EBV genotype in the LMP-2A gene was thus demonstrated as being correlated with the host's geographical location. Typing in the EBV-associated nuclear antigen 2 gene was not related to that in the LMP-2A gene. Detection of the EBV genotype in the LMP-2A gene may be useful for determining the geographical origins of unidentified cadavers.
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Affiliation(s)
- Hiroshi Ikegaya
- National Research Institute of Police Science, Chiba 277-0882, Japan.
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26
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Ikegaya H. Geographical identification of cadavers by human parasites. Forensic Sci Int Genet 2007; 2:83-90. [PMID: 19083803 DOI: 10.1016/j.fsigen.2007.10.184] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2007] [Accepted: 10/10/2007] [Indexed: 12/31/2022]
Abstract
Increasing numbers of unidentified cadavers have recently become an important forensic problem in many countries. To identify such cadavers, DNA typing method is widely used. However, as this technique requires reference DNA samples, a method that would quickly narrow down possible candidates for the cadavers is needed to enable rapid identification. Unfortunately, no really reliable methods suitable for this purpose have been available; however, methods using the human parasites, JC virus, BK virus and EB virus, have been reported. These new methods narrow down the candidates by elucidating geographic origins. Though not detectable in all cases, results using such methods with several parasites have enabled us to estimate geographic origins of unidentified cadavers with a high detection rate.
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Affiliation(s)
- Hiroshi Ikegaya
- National Research Institute of Police Science, Kashiwa, Chiba, Japan.
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MUELLER NANCYE, BIRMANN BRENDAM, PARSONNET JULIE, SCHIFFMAN MARKH, STUVER SHERRIO. Infectious Agents. CANCER EPIDEMIOLOGY AND PREVENTION 2006:507-548. [DOI: 10.1093/acprof:oso/9780195149616.003.0026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
AbstractThere is substantial evidence that infectious agents play a causal role in a variety of human malignancies. These cancers include the liver, cervix, stomach, nasopharynx, bladder, and bile duct as well as Kaposi sarcoma (KS) and several lymphomas. This chapter summarizes the biological and epidemiologic features of each of the major oncogenic infections, beginning with the viruses, followed by H. pylori, and with a brief summary of the relevant parasites.
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Szkaradkiewicz A, Majewski W, Wal M, Czyzak M, Majewski P, Bierła J, Kuch A. Epstein-Barr virus (EBV) infection and p53 protein expression in gastric carcinoma. Virus Res 2006; 118:115-9. [PMID: 16413625 DOI: 10.1016/j.virusres.2005.12.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2005] [Revised: 11/29/2005] [Accepted: 12/04/2005] [Indexed: 12/29/2022]
Abstract
In the presented studies p53 protein expression was evaluated in samples of gastric carcinoma originating from 32 selected adult patients (with documented diagnosis of adenocarcinoma of the stomach and without the presence of Helicobacter pylori infection). Among the patients 14 individuals carried EBV-positive gastric carcinoma (group 1) while the 18 remaining patients carried EBV-negative gastric carcinoma (group 2). EBV infection was detected testing the tissue material for the presence of EBER by RNA in situ hybridization (ISH) and testing sera of the patients for EBV-specific antibodies. Expression of p53 protein was analysed using immunohistochemistry. Presence of p53 protein was noted in 9 (64.3%) cases of EBV-positive gastric cancer (group 1) and in 10 (55.5%) cases of EBV-negative gastric cancer (group 2). No significant differences were detected in the frequencies of p53 protein expression in the two studied groups. The results permit to conclude that abnormalities in p53 in gastric cancer are independent of EBV infection, even if EBV may participate in development of the tumour.
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29
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Kalkan A, Ozdarendeli A, Bulut Y, Yekeler H, Cobanoglu B, Doymaz MZ. Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin- embedded breast cancer tissues. Med Princ Pract 2005; 14:268-71. [PMID: 15961939 DOI: 10.1159/000085748] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2004] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE To investigate etiological role of Epstein-Barr virus (EBV) DNA in breast cancer. MATERIALS AND METHODS The presence of EBV DNA in 57 breast cancer tissues was investigated with a sensitive PCR assay. The breast cancer tissues were from invasive ductular (n=28), lobular (n=20) and other miscellaneous carcinomas (n=9). Tissues from normal breasts and patients with various benign breast diseases (n=55): fibrocystic disease (n=34), fibroadenoma (n=16), hyperplasia, and granulomatous mastitis (n=5), were used as control samples. RESULTS EBV DNA was detected in 13 (23%) cancerous tissues (7 ductular, 4 lobular, 2 other carcinoma) and 19 (35%) in the control tissues. The difference between EBV presence in malignant and benign tissues was not statistically significant (p>0.05). CONCLUSION The presence of EBV DNA was detected almost equally in both breast cancer and normal tissues, which indicates no etiological role for EBV in breast cancer. We suggest further etiological studies.
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Affiliation(s)
- Ahmet Kalkan
- Department of Infectious Diseases, Firat University Medical School, Elazig, Turkey.
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Trimeche M, Ziadi S, De Leval L, Hmissa S, Sriha B, Mokni M, Toumi I, Elomri H, Laatiri A, Kehlif A, Boniver J, Korbi S. [Prevalence of Epstein-Barr virus in non-Hodgkin's lymphomas in central region of Tunisia]. Ann Pathol 2005; 25:95-102. [PMID: 16142160 DOI: 10.1016/s0242-6498(05)86172-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The purpose of this study was to evaluate the prevalence of EBV in non-Hodgkin's lymphomas occuring in non-immunocopromised patients in Tunisia through a series of 126 cases. EBV was investigated by EBER oligonucleotide in situ hybridization (ISH) and LMP1-immunohistochemistry. Serological study of EBV has been performed before therapy in 28 patients. EBV was detected in tumor cells by ISH in 28/126 (22.2%) cases. Variable proportions of tumor cells were positive. LMP1 was identified in only 8 cases. EBV was more frequently observed in T-cell lymphomas (9/24 patients; 37.5%) than in B-cell lymphomas (19/102 patients; 18.6%) (p=0.04). There was a strong relationship between EBV and small intestine lymphomas (6/8 patients; 75%) and T/NK nasal type lymphomas (3/3 patients; 100%). EBV serological reactivation was noted in 7/13 patients in clinical stages III/IV and in only 1/10 patients in stages I/II (p=0.03). In conclusion, the prevalence of EBV in Tunisian non-Hodgkin's lymphomas is low but variable depending on the histological type and anatomical location with a predilection for small intestine and nasal lymphomas.
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Affiliation(s)
- Mounir Trimeche
- Laboratoire d'Anatomie et de Cytologie Pathologiques, CHU Farhat Hached, 4000 Sousse, Tunisia
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Alipov G, Nakayama T, Nakashima M, Wen CY, Niino D, Kondo H, Pruglo Y, Sekine I. Epstein-Barr virus-associated gastric carcinoma in Kazakhstan. World J Gastroenterol 2005; 11:27-30. [PMID: 15609391 PMCID: PMC4205378 DOI: 10.3748/wjg.v11.i1.27] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the incidence of Epstein-Barr virus-associated gastric cancer (EBV-GC) in Kazakhstan and to compare it with that in Russia, Western and Asian countries in order to evaluate the significance of epidemiopathologic and ethnic factors.
METHODS: In situ hybridization (ISH) of EBV-encoded small RNA-1 (EBER-1) was used to identify the presence of EBER-1 signal in 139 formalin-fixed and paraffin-embedded GC tissues from Kazakhstan.
RESULTS: EBER-1 expression was observed in the nuclei of 10% of the cases of GC (14/139), but not in the surrounding normal mucosa. The incidence of the diffuse type of EBV-GC was significantly higher in Kazakhstan (14%, 13/91) than that of the intestinal type (2%, 1/48). Furthermore, the incidence was significantly higher in males (14%, 12/89) than in females (3.7%, 2/53) from all countries. The overall incidence of EBV-GC increased from 6.7% in Asian countries to 8.7% in Russia, 10.1% in Kazakhstan and 16% in Western countries.
CONCLUSION: Geographical differences in the incidence of EBV-GC may reflect the epidemiologic factors and/or dietary habits independent of histological type and sex.
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Affiliation(s)
- Gabit Alipov
- Division of Scientific Data Regsitry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Abstract
An association between viral infection, particularly the human papillomavirus, and the development of esophageal carcinoma (EC) has been reported. However, reports concerning the relationship between herpes simplex virus (HSV) and Epstein-Barr virus (EBV) with EC are few. There are geographic variations in infection rates. This study was aimed to determine the co-incidence of infection of the two viruses' with esophageal carcinoma and the differentiation of cancer tissues and lymphocytes infiltration in the tumor stroma of the high-incidence area of Shantou China. To determine the association between viral infection (HSV and EBV) and EC, we applied in situ hybridization (ISH) and immunohistochemistry (IHC) in 164 esophageal carcinoma surgical specimens from the high-incidence area of Shantou China. HSV DNA and HSVI, II protein expression were found in 52 (31.7%) of the 164 tumors; EBV EBER and LMP-1 proteins were identified in only 10 (6.1%) carcinoma specimens by in situ hybridization and immunohistochemistry. In histopathology analysis, the positive cases of HSV appeared to be more predominant in well and moderately differentiated squamous cell carcinomas, and the positive cases of EBV were found in poorly differentiated squamous cell carcinomas or undifferentiated carcinomas with intense lymphoid infiltration. Our results confirm the involvement of HSV and EBV in esophageal carcinomas and the relationship between HSV and EBV infection and esophageal carcinoma cell differentiation with lymphocyte infiltration in the tumor stroma. However, the two herpes viruses, HSV and EBV, particularly the human HSV may be one of the etiological factors in development of this malignancy among the high-incidence population of Shantou China.
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Affiliation(s)
- Ming-yao Wu
- Department of Pathology, Shantou University Medical College, 22 Xinling Road, Shantou 515031, Guangdong, Province, China.
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Goldenberg D, Benoit NE, Begum S, Westra WH, Cohen Y, Koch WM, Sidransky D, Califano JA. Epstein-Barr virus in head and neck cancer assessed by quantitative polymerase chain reaction. Laryngoscope 2004; 114:1027-31. [PMID: 15179207 DOI: 10.1097/00005537-200406000-00013] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES/HYPOTHESIS Epstein-Barr virus (EBV) has classically been associated with nasopharyngeal carcinoma and Burkitt's lymphoma. Recently, multiple studies have been published linking EBV with oral squamous cell carcinoma and, to a lesser extent, hypopharyngeal and laryngeal tumors. Using a sensitive method of detection, the authors sought to analyze the presence and quantity of EBV DNA in a large cohort of head and neck cancers. STUDY DESIGN : Retrospective cohort study. METHODS Three hundred head and neck cancer samples exclusive of nasopharyngeal carcinoma were examined for the presence of EBV using quantitative polymerase chain reaction. Eighty-four tumor samples from the larynx, 30 from the hypopharynx, 73 from the oropharynx, and 113 from the oral cavity were analyzed for EBV quantity, which was expressed as the number of viral copies per cell genome. Representative samples, which contained the highest EBV DNA levels, were examined using in situ hybridization. Results were correlated with tumor grade and site and tobacco and alcohol exposure. RESULTS Three of 300 (1%) tumor samples were overtly positive for EBV DNA (defined as >0.1 copies of viral DNA/cell genome). Five of 300 (2%) tumor samples showed low levels (defined as >0.01 and <0.1 copies of viral DNA/cell genome), and 68 of 300 tumor samples (23%) showed trace levels (defined as < 0.01 copies of viral DNA/cell genome) of EBV DNA. No correlation was found between EBV positivity and tobacco exposure, alcohol exposure, or tumor grade. CONCLUSION In the overwhelming majority of head and neck cancers in this North American cohort, EBV did not appear to contribute to growth of a dominant clonal population with integrated EBV genome and was unlikely to be a genetic etiological agent in tumor development. The low quantities of EBV detected in a minority of head and neck cancers may be related to the presence of EBV genome in rare lymphoid or epithelial cells adjacent to the primary head and neck cancer.
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Affiliation(s)
- David Goldenberg
- Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Lundell R, Elenitoba-Johnson KSJ, Lim MS. T-cell Posttransplant Lymphoproliferative Disorder Occurring in a Pediatric Solid-organ Transplant Patient. Am J Surg Pathol 2004; 28:967-73. [PMID: 15223970 DOI: 10.1097/00000478-200407000-00019] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication seen in transplant patients as a consequence of immunosuppressant therapy. Most cases are of B-cell origin and are commonly associated with Epstein-Barr virus (EBV) infection. T-cell PTLDs are rare and only 13 pediatric T-cell PTLDs with clinicopathologic correlation have been reported previously. We present the histologic, immunophenotypic, and molecular features of a monomorphic PTLD (T-cell lymphoma) identified in a pediatric patient following orthotopic liver transplantation. The lymphoma was identified in the ileum, rectum, and mesenteric lymph nodes. In situ hybridization revealed numerous EBER-1-positive tumor cells. A current review of the literature is also discussed. Of the 14 cases of pediatric T-cell PTLD reported in the literature, only 3 (21.4%) are described as being EBV positive. Most of the reported PTLDs are monoclonal, with 9 of 11 cases (82%) showing a clonal T-cell population by gene rearrangement studies. T-cell PTLD cases appear to have a poor prognosis (11 of 14 patients died of the disease), although patients with involvement of specific anatomic sites may have a better outcome.
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Affiliation(s)
- Ryan Lundell
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
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35
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Holm R. In Situ Hybridization Methods to Study Microbial Populations and Their Interactions with Human Host Cells. J Microbiol Methods 2004. [DOI: 10.1016/s0580-9517(04)34001-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Karajannis MA, Hummel M, Oschlies I, Anagnostopoulos I, Zimmermann M, Stein H, Parwaresch R, Reiter A. Epstein-Barr virus infection in Western European pediatric non-Hodgkin lymphomas. Blood 2003; 102:4244. [PMID: 14623773 DOI: 10.1182/blood-2003-08-2986] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Duraiswamy J, Burrows JM, Bharadwaj M, Burrows SR, Cooper L, Pimtanothai N, Khanna R. Ex vivo analysis of T-cell responses to Epstein-Barr virus-encoded oncogene latent membrane protein 1 reveals highly conserved epitope sequences in virus isolates from diverse geographic regions. J Virol 2003; 77:7401-10. [PMID: 12805439 PMCID: PMC164808 DOI: 10.1128/jvi.77.13.7401-7410.2003] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Epstein-Barr virus (EBV)-encoded oncogene latent membrane protein (LMP) 1, which is consistently expressed in multiple EBV-associated malignancies, has been proposed as a potential target antigen for any future vaccine designed to control these malignancies. However, the high degree of genetic variation in the LMP1 sequence has been considered a major impediment for its use as a potential immunotherapeutic target for the treatment of EBV-associated malignancies. In the present study, we have employed a highly efficient strategy, based on ex vivo functional assays, to conduct an extensive sequence-wide analysis of LMP1-specific T-cell responses in a large panel of healthy virus carriers of diverse ethnic origin and nasopharyngeal carcinoma patients. By comparing the frequencies of T cells specific for overlapping peptides spanning LMP1, we mapped a number of novel HLA class I- and class II-restricted LMP1 T-cell epitopes, including an epitope with dual HLA class I restriction. More importantly, extensive sequence analysis of LMP1 revealed that the majority of the T-cell epitopes were highly conserved in EBV isolates from Caucasian, Papua New Guinean, African, and Southeast Asian populations, while unique geographically constrained genetic variation was observed within one HLA A2 supertype-restricted epitope. These findings indicate that conserved LMP1 epitopes should be considered in designing epitope-based immunotherapeutic strategies against EBV-associated malignancies in different ethnic populations.
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Affiliation(s)
- Jaikumar Duraiswamy
- Cooperative Research Centre for Vaccine Technology, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Department of Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia 4029
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Irie HY, Jaklitsch MT, Shaffer K, Weinstein M, Salgia R. Unusual problems in breast cancer and a rare lung cancer case. Case 4. Primary lymphoepithelioma-like carcinoma of the lung. J Clin Oncol 2003; 21:2220-2. [PMID: 12775751 DOI: 10.1200/jco.2003.09.088] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Hanna Y Irie
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, USA
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Krugmann J, Tzankov A, Gschwendtner A, Fischhofer M, Greil R, Fend F, Dirnhofer S. Longer failure-free survival interval of Epstein-Barr virus-associated classical Hodgkin's lymphoma: a single-institution study. Mod Pathol 2003; 16:566-73. [PMID: 12808062 DOI: 10.1097/01.mp.0000071843.09960.bf] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
We analyzed Epstein-Barr virus association in classical Hodgkin's lymphoma from a single center in Austria with special emphasis on the latent membrane protein1 gene configuration and clinical outcome. All 119 (65 male, 54 female) patients were treated from 1974 to 1999 in the Division of Hematology and Oncology at the Department of Internal Medicine, University of Innsbruck, Austria. The mean follow-up time was 122 months (range, 3-333 mo). Epstein-Barr virus was examined by latent membrane protein1 immunohistochemistry and by in situ hybridization for Epstein-Barr virus-encoded early ribonuclein acid transcripts. For assessment of the Epstein-Barr virus subtype (A/B) and latent membrane protein1 gene configuration, the polymerase chain reaction was employed. Fifty-four reactive tonsils were used as the control population. These results as well as clinical parameters such as age, gender, tumor stage, risk factors, and B symptoms were correlated with failure-free and overall survival. Latent membrane protein1 was detected in 31/119 (26%) classical Hodgkin's lymphoma, and Epstein-Barr virus subtyping was successful in 19 of the 31 virus-infected classical Hodgkin's lymphoma cases, as well as in 28 of 54 reactive tonsils. Subtype A was observed in all classical Hodgkin's lymphoma patients and in 26/28 (93%) tonsils. The 30-base pair latent membrane protein1 gene deletion was found in only 4/31 (13%) Epstein-Barr virus-associated classical Hodgkin's lymphoma as well as in 20/54 (37%) reactive tonsils. Patients with Epstein-Barr virus-associated classical Hodgkin's lymphoma showed a significantly longer mean time to first relapse of 99 months, as compared with 49 months for the Epstein-Barr virus-negative cases (P <.02), and were more frequent in those aged >45 years (P <.04). Epstein-Barr virus-associated classical Hodgkin's lymphoma were predominantly of the mixed-cellularity subtype and occurred more frequently in male patients, in patients with Stage III and IV, and in patients with B symptoms as well as risk factors. However, overall survival did not correlate with Epstein-Barr virus association. The 30-base pair latent membrane protein1 gene deletion had no influence on overall survival and failure-free survival time. Although the number of patients with this specific mutation was low, it further shows that an increased oncogenic potential of the latent membrane protein1 deletion variant is unlikely. This large single-center study demonstrates a low prevalence of Epstein-Barr virus positivity in classical Hodgkin's lymphoma in western Europe. In accordance with results of similar studies, the presence of Epstein-Barr virus has a beneficial effect on the length of failure-free survival despite the higher frequency of risk factors such as higher tumor stage or advanced age.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antigens, Viral/genetics
- Antigens, Viral/metabolism
- Biomarkers, Tumor/metabolism
- Child
- Child, Preschool
- Disease-Free Survival
- Epstein-Barr Virus Infections/complications
- Epstein-Barr Virus Infections/metabolism
- Epstein-Barr Virus Infections/pathology
- Female
- Herpesvirus 4, Human/classification
- Herpesvirus 4, Human/genetics
- Herpesvirus 4, Human/isolation & purification
- Hodgkin Disease/metabolism
- Hodgkin Disease/pathology
- Hodgkin Disease/virology
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Polymerase Chain Reaction
- RNA, Neoplasm/analysis
- RNA, Viral/analysis
- Retrospective Studies
- Viral Matrix Proteins/genetics
- Viral Matrix Proteins/metabolism
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Affiliation(s)
- Jens Krugmann
- Institute of Pathology, University of Innsbruck, Austria
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40
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Hayashi K, Jin Z, Onoda S, Joko H, Teramoto N, Ohara N, Oda W, Tanaka T, Liu YX, Koirala TR, Oka T, Kondo E, Yoshino T, Takahashi K, Akagi T. Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS. THE AMERICAN JOURNAL OF PATHOLOGY 2003; 162:1721-36. [PMID: 12707056 PMCID: PMC1851174 DOI: 10.1016/s0002-9440(10)64306-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.
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Affiliation(s)
- Kazuhiko Hayashi
- Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
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41
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Zhang Y, Molot R. Severe gastritis secondary to Epstein-Barr viral infection. Unusual presentation of infectious mononucleosis and associated diffuse lymphoid hyperplasia in gastric mucosa. Arch Pathol Lab Med 2003; 127:478-80. [PMID: 12683879 DOI: 10.5858/2003-127-0478-sgstev] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Infectious mononucleosis is usually a self-limited clinical syndrome caused by primary Epstein-Barr virus infection. It is occasionally compounded by severe complications involving many different organ systems. Predominant gastrointestinal involvement is rarely documented. We present an unusual case of acute Epstein-Barr virus infection-associated gastritis with diffuse atypical lymphoid hyperplasia in gastric mucosa. The clinical, radiographic, histopathologic, immunohistochemical, and in situ hybridization features needed for accurate diagnosis and differentiation from gastric malignancies are discussed.
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Affiliation(s)
- Yanlong Zhang
- Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison, Wis, USA
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42
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Meier C. cycloSal-Pronucleotides—Design of the Concept, Chemistry, and Antiviral Activity. ACTA ACUST UNITED AC 2003. [DOI: 10.1016/s1075-8593(03)04006-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023]
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43
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Martorell MA, Julian JM, Calabuig C, García-García JA, Pérez-Vallés A. Lymphoepithelioma-like carcinoma of the uterine cervix. Arch Pathol Lab Med 2002; 126:1501-5. [PMID: 12456211 DOI: 10.5858/2002-126-1501-llcotu] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT It has been proposed that Epstein-Barr virus (EBV) plays a role in the etiology of lymphoepithelioma-like carcinoma (LELC) in diverse anatomic locations. In contrast to Asian women, Western women have a low prevalence of LELC of the uterine cervix, and EBV genomes have not been identified. OBJECTIVE To assess the presence of EBV in LELC of the uterine cervix in 4 white Western women. DESIGN We collected 4 cases of LELC of the uterine cervix between 1990 and 2000. We performed histologic and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. We amplified tumor DNA with polymerase chain reaction to detect EBV, human papillomavirus, and simian virus 40 DNAs. RESULTS Immunohistochemically, tumor cells were positive for cytokeratins and showed strong expression of p53 and MIB-1. Staining for the oncoprotein c-Erb-B2 was focally positive, and staining for Bcl-2 and progesterone receptors was negative. Only one case showed focal nuclear staining for estrogen receptors. All cases had a dense infiltrate of mature lymphocytes expressing T-cell antigens CD45RO, CD3, and CD8. Polymerase chain reaction analysis did not detect EBV, human papillomavirus, or simian virus 40 DNA sequences in any of the 4 cases. One case had positive serologic results for anti-EBV antibodies, indicating a mild or chronic infection. CONCLUSIONS LELC of the uterine cervix shows the immunohistochemical profile of an aggressive tumor in spite of its good prognosis, in which CD8 cytotoxic suppressor lymphocytes could play an important role. Based on our results, the role of EBV, human papillomavirus, or simian virus 40 in the pathogenesis of LELC of the uterine cervix in Western women remains unclear.
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Affiliation(s)
- Miguel A Martorell
- Servicio Anatomía Patológica, Hospital General Universitario, Valencia, Spain.
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44
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Kassis J, Maeda A, Teramoto N, Takada K, Wu C, Klein G, Wells A. EBV-expressing AGS gastric carcinoma cell sublines present increased motility and invasiveness. Int J Cancer 2002; 99:644-51. [PMID: 12115496 DOI: 10.1002/ijc.10382] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Tumor invasion marks a critical point in cancer progression; it is a harbinger of morbidity and mortality. Thus, the cellular events that enable the invasive phenotype are under intense investigation. Epstein-Barr virus (EBV) is associated with a number of cancers, including Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) and is suspected to contribute to their tumorigenesis. On average, 8% of gastric carcinomas have been shown to carry this virus. To explore whether the presence of EBV in gastric carcinoma contributes to tumor progression in this predominantly invasive carcinoma, we examined a panel of 2 in vitro EBV-infected human gastric cancer cell line sublines and their mock-infected AGS parental control line. We found EBV infection caused a marked increase in transmigration of a Matrigel barrier (415% and 303%, p < 0.05, for the 2 infected lines). This correlated with increased motility of these sublines (233% and 140%, p < 0.05). As this pattern of increased motility leading to a more pronounced enhancement of invasion has been noted in other tumor cells, we explored the roles of autocrine signaling pathways previously implicated in carcinoma motility and invasion. Inhibitors to the epidermal growth factor receptor (EGFR) (PD153035), phospholipase C (PLC) (U73122), extracellular-signal regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) (PD089035) and PI-3 kinase (Wortmannin) were not informative. These data suggest that EBV increases migration of AGS cells by a mechanism independent of these autocrine growth factor-induced pathways. Instead, we found that the EBV-infected cells presented increased focal adhesion kinase (FAK) phosphorylation. These findings suggest a role for integrin-mediated signaling in promoting EBV-associated invasiveness.
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Affiliation(s)
- Jareer Kassis
- Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, PA, USA
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45
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Wroblewski JM, Copple A, Batson LP, Landers CD, Yannelli JR. Cell surface phenotyping and cytokine production of Epstein-Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCLs). J Immunol Methods 2002; 264:19-28. [PMID: 12191505 DOI: 10.1016/s0022-1759(01)00565-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Epstein-Barr Virus-transformed B lymphoblastoid cell lines (EBV-LCLs) are routinely used for the in vitro expansion of T cells. However, these cell lines are reported to produce the cytokine IL-10, which is inhibitory for T cells. We, therefore, characterized a panel of 37 EBV-LCLs for a variety of cell surface markers, for secretion of various cytokines including IL-10 and for immunoglobulin production. These cell lines were derived from normal donors or patients with nonsmall cell lung cancer, acute myelogenous leukemia, melanoma or colon cancer. Overall, 26 lines were positive for CD19 and CD20, and 11 were negative for both. All of the lines were strongly HLA-DR+, while CD40 expression was variable. Twenty-four (65%) were both CD23+ and secreted immunoglobulin, and 33 expressed kappa and/or lambda light chains. Additionally, all of the EBV-LCLs were negative for T cell (CD3), NK cell (CD16, CD56), monocyte (CD14) and granulocyte (CD66b) surface markers. Some level of IL-10, IL-6, IL-12p40 and TNF-alpha cytokine production was detected in 33, 18, 19 and 12 EBV-LCLs, respectively. Together, these data reflect the heterogeneity of EBV-LCLs, which cautions their use nondiscriminately in various immunologic assays.
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MESH Headings
- Animals
- Antigens, Differentiation, B-Lymphocyte/analysis
- B-Lymphocytes/immunology
- B-Lymphocytes/metabolism
- B-Lymphocytes/virology
- Callithrix
- Cell Line, Transformed/immunology
- Cell Line, Transformed/metabolism
- Cell Line, Transformed/virology
- Cytokines/biosynthesis
- Dose-Response Relationship, Immunologic
- Gene Expression Regulation, Viral
- Herpesvirus 4, Human/genetics
- Herpesvirus 4, Human/physiology
- Humans
- Immunoglobulins/biosynthesis
- Immunophenotyping/methods
- Interleukin-10/biosynthesis
- Lymphocyte Activation/genetics
- Tumor Cells, Cultured
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Affiliation(s)
- Joanne M Wroblewski
- Division of Hematology and Oncology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
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46
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Fukayama M, Chong JM, Uozaki H. Pathology and molecular pathology of Epstein-Barr virus-associated gastric carcinoma. Curr Top Microbiol Immunol 2002; 258:91-102. [PMID: 11443869 DOI: 10.1007/978-3-642-56515-1_6] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- M Fukayama
- Department of Pathology, Faculty of Medicine, Tokyo University, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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47
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Plaza G, Manzanal AI, Fogué L, Santón A, Martínez-Montero JC, Bellas C. Association of Epstein-Barr virus and nasopharyngeal carcinoma in Caucasian patients. Ann Otol Rhinol Laryngol 2002; 111:210-6. [PMID: 11913680 DOI: 10.1177/000348940211100304] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We evaluated the association of nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) in Spanish patients, and studied the expression of EBV products (latent membrane protein-1 [LMP-1] and ZEBRA proteins) by NPC cells and its possible prognostic value. In situ hybridization (ISH) for EBV-encoded nonpolyadenylated RNAs (EBERs) and immunohistochemical expression of LMP-1 and ZEBRA proteins by immunohistochemistry were examined in formalin-fixed, paraffin-embedded NPC specimens from 30 patients, and a survival analysis was done by the Kaplan-Meier method. We detected EBERs by ISH in 96.67% of the NPC cases, and detected expression of LMP-I in 43.33% of the NPC cases and expression of ZEBRA protein in 6.67% of the NPC cases. We conclude that ISH for expression of EBERs is an adequate method for detection of EBV in NPC. LMP-1 is not frequently expressed in NPC cells (43.33%). Most NPC cells carry a latent EBV infection. LMP-1 expression might have worsened the prognosis of NPC in our series.
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Affiliation(s)
- Guillermo Plaza
- Otolaryngology Department, Ramón y Cajal Hospital, University of Alcalá, Madrid, Spain
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48
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Meerbach A, Gruhn B, Egerer R, Reischl U, Zintl F, Wutzler P. Semiquantitative PCR analysis of Epstein-Barr virus DNA in clinical samples of patients with EBV-associated diseases. J Med Virol 2001; 65:348-57. [PMID: 11536243 DOI: 10.1002/jmv.2040] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The laboratory diagnosis of primary and reactivated Epstein-Barr virus (EBV) infection is based on serologic methods in immunocompetent patients. However, in immunocompromised patients, serologic data are difficult to interpret and do not often correlate with clinical data. In order to find a useful and practical marker for diagnosis of EBV-related diseases, a polymerase chain reaction (PCR) assay was established for semiquantitative detection of EBV sequences. The method was based on a nested PCR, using primers of the virus capsid antigen p23 region and an endpoint dilution. This method was carried out on 68 plasma samples, 68 samples of peripheral blood mononuclear cells and 5 cerebrospinal fluid samples of 39 patients with various diseases to evaluate the EBV-genome copy number. Samples from patients suffering from infectious mononucleosis served as positive controls for active EBV infection. In 5 patients with infectious mononucleosis, high copy numbers of EBV genomes in peripheral blood mononuclear cells were detected within a range of 1,000-40,000 copies in 10(5) peripheral blood mononuclear cells. In contrast, samples from 19 latently infected persons either showed low copy numbers (10-100 in 10(5) peripheral blood mononuclear cells) or were EBV PCR negative. Comparable results were observed in seven renal transplant patients without any symptoms. The practical value of the semiquantitative detection of EBV DNA was demonstrated in three bone marrow transplant recipients. Two developed a lymphoproliferative disease associated with extremely high amounts of EBV DNA in plasma (16,000 and 50,000 copies/ml, respectively) and peripheral blood mononuclear cells (100,000 and 6.5 million copies in 10(5) peripheral blood mononuclear cells, respectively). The high EBV load in plasma and peripheral blood mononuclear cells was reduced dramatically after successful antiviral therapy in one case. The third bone marrow transplant recipient developed an EBV-induced transverse myelitis with an increased number of EBV-genome copies in peripheral blood mononuclear cells and EBV-positive cerebrospinal fluid samples. After combined antiviral and immune therapy, the EBV-genome copy numbers decreased and the patient recovered completely. These data demonstrate a good correlation between semiquantitative detection of EBV genomes and clinical findings. The method is recommended for the diagnosis of EBV-associated diseases in patients after transplantation, as well as for monitoring the response to therapy.
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Affiliation(s)
- A Meerbach
- Institute for Antiviral Chemotherapy, University of Jena, Jena, Germany.
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49
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Castro CY, Ostrowski ML, Barrios R, Green LK, Popper HH, Powell S, Cagle PT, Ro JY. Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. Hum Pathol 2001; 32:863-72. [PMID: 11521232 DOI: 10.1053/hupa.2001.26457] [Citation(s) in RCA: 99] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.
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Affiliation(s)
- C Y Castro
- Division of Pathology, the University of Texas M.D. Anderson Cancer Center, Baylor College of Medicine, Houston, TX, USA
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50
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Collins MH, Montone KT, Leahey AM, Hodinka RL, Salhany KE, Belchis DA, Tomaszewski JE. Autopsy pathology of pediatric posttransplant lymphoproliferative disorder. Pediatrics 2001; 107:E89. [PMID: 11389287 DOI: 10.1542/peds.107.6.e89] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death. METHODS Postmortem examinations were performed on 7 patients after bone marrow (n = 3) or liver (n = 4) transplant. PTLD was classified histologically as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used to categorize infections as negative, primary, or reactive. RESULTS PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before death, and 1.5 to 4 (mean: 3) months after transplant; PTLD was diagnosed in 2 cases at autopsy 2.5 and 4 months after transplant. Postmortem PTLD histology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperplasia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not have EBV serology that indicated active infection. Complete autopsy of 4 patients who died with biopsy-proven PTLD revealed widely disseminated disease, and lymph node, brain, gastrointestinal tract, and kidney were involved in all 4 patients. Cases diagnosed at autopsy were 1 widely disseminated PTLD that had been suspected but not proven antemortem, and 1 PTLD confined to abdominal lymph nodes that was not suspected antemortem. Severe organ dysfunction (renal failure, gastrointestinal hemorrhage) was caused by massive PTLD infiltration in 2 patients. The conditions other than PTLD that contributed to morbidity and death were organ infection (5 cases), infarcts (4 cases), and diffuse alveolar damage (3 cases). CONCLUSIONS PTLD may occur within weeks after transplant in children. The distribution of PTLD comprises a spectrum from localized and subclinical to widely disseminated and symptomatic. PTLD may cause demise quickly after the onset of signs and symptoms, through massive organ infiltration or associated conditions, such as diffuse alveolar damage. EBV serology may not accurately reflect the presence or extent of PTLD. Autopsy studies of transplant patients are necessary to identify the true incidence, natural history, and response to treatment of PTLD.
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Affiliation(s)
- M H Collins
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
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