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Integrated Microarray-Based Data Analysis of miRNA Expression Profiles: Identification of Novel Biomarkers of Cisplatin-Resistance in Testicular Germ Cell Tumours. Int J Mol Sci 2023; 24:ijms24032495. [PMID: 36768818 PMCID: PMC9916636 DOI: 10.3390/ijms24032495] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/13/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Testicular germ cell tumours (TGCTs) are the most common solid malignancy among young men, and their incidence is still increasing. Despite good curability with cisplatin (CDDP)-based chemotherapy, about 10% of TGCTs are non-responsive and show a chemoresistant phenotype. To further increase TGCT curability, better prediction of risk of relapse and early detection of refractory cases is needed. Therefore, to diagnose this malignancy more precisely, stratify patients more accurately and improve decision-making on treatment modality, new biomarkers are still required. Numerous studies showed association of differential expressions of microRNAs (miRNAs) with cancer. Using microarray analysis followed by RT-qPCR validation, we identified specific miRNA expression patterns that discriminate chemoresistant phenotypes in TGCTs. Comparing CDDP-resistant vs. -sensitive TGCT cell lines, we identified miR-218-5p, miR-31-5p, miR-125b-5p, miR-27b-3p, miR-199a-5p, miR-214-3p, let-7a and miR-517a-3p as significantly up-regulated and miR-374b-5p, miR-378a-3p, miR-20b-5p and miR-30e-3p as significantly down-regulated. In patient tumour samples, we observed the highest median values of relative expression of miR-218-5p, miR-31-5p, miR-375-5p and miR-517a-3p, but also miR-20b-5p and miR-378a-3p, in metastatic tumour samples when compared with primary tumour or control samples. In TGCT patient plasma samples, we detected increased expression of miR-218-5p, miR-31-5p, miR-517a-3p and miR-375-5p when compared to healthy individuals. We propose that miR-218-5p, miR-31-5p, miR-375-5p, miR-517-3p, miR-20b-5p and miR-378a-3p represent a new panel of biomarkers for better prediction of chemoresistance and more aggressive phenotypes potentially underlying metastatic spread in non-seminomatous TGCTs. In addition, we provide predictions of the targets and functional and regulatory networks of selected miRNAs.
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Lembeck AL, Puchas P, Hutterer G, Barth DA, Terbuch A, Bauernhofer T, Pichler M. MicroRNAs as Appropriate Discriminators in Non-Specific Alpha-Fetoprotein (AFP) Elevation in Testicular Germ Cell Tumor Patients. Noncoding RNA 2020; 6:ncrna6010002. [PMID: 31906360 PMCID: PMC7151547 DOI: 10.3390/ncrna6010002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 12/09/2019] [Accepted: 12/28/2019] [Indexed: 02/07/2023] Open
Abstract
Testicular germ cell tumors (TGCTs) are the most commonly diagnosed malignancies in younger men. The monitoring of disease course and recurrence is supported by traditional tumor markers, including α-fetoprotein (AFP). AFP is physiologically synthesized in the liver and can be detected at increased levels in testicular cancer patients as well as under other benign liver diseases, which have been reported as a misleading cause of interpretation of TGCTs clinical course. A cluster of stem cell-associated microRNAs has been reported to outperform traditional tumor markers in newly diagnosed TGCTs, but the value of these microRNAs to differentiate between specific and unspecific AFP elevations, has never been reported. We report here a patient with chronic hepatitis B and normal liver related blood values presenting with a surgically removed primary TGCT and elevated AFP levels. Clinical staging revealed a suspect retroperitoneal metastatic lymph node together with other risk factors and first line treatment with PEB chemotherapy was administered. During curative treatment significantly rising AFP levels led to the assumption of chemo-resistant disease, mandating the initiation of salvage chemotherapy and surgical removal of the putative lymph node metastases. The AFP levels continuously decreased with the interruption of chemotherapeutic agents, indicating a chemotherapy-induced liver toxicity on the basis of pre-existing liver disease. MiR-371a-3p serum levels were not detectable in serum samples with elevated AFP levels. In conclusion, miR-371a-3p may be a reliable biomarker to differentiate between non-specific AFP elevations in TGCTs patients.
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Affiliation(s)
- Anna L. Lembeck
- Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (A.L.L.); (P.P.); (D.A.B.); (A.T.); (T.B.)
| | - Philip Puchas
- Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (A.L.L.); (P.P.); (D.A.B.); (A.T.); (T.B.)
| | - Georg Hutterer
- Department of Urology, Medical University of Graz, 8036 Graz, Austria;
| | - Dominik A. Barth
- Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (A.L.L.); (P.P.); (D.A.B.); (A.T.); (T.B.)
| | - Angelika Terbuch
- Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (A.L.L.); (P.P.); (D.A.B.); (A.T.); (T.B.)
| | - Thomas Bauernhofer
- Division of Oncology, Medical University of Graz, 8036 Graz, Austria; (A.L.L.); (P.P.); (D.A.B.); (A.T.); (T.B.)
| | - Martin Pichler
- Division of Oncology and Research Unit for Non-Coding RNA and Genome Editing, Medical University of Graz, 8036 Graz, Austria
- Correspondence:
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Gurakar A, Ma M, Garonzik-Wang J, Kim A, Anders RA, Oshima K, Georgiades C, Gurakar M, Ottmann S, Cameron AM, Philosophe B, Saberi B. Clinicopathological Distinction of Low-AFP-Secreting vs. High-AFP-Secreting Hepatocellular Carcinomas. Ann Hepatol 2018; 17:1052-1066. [PMID: 31208632 DOI: 10.5604/01.3001.0012.7206] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 08/07/2018] [Indexed: 02/04/2023]
Abstract
Ilntroduction and aims. We aimed to investigate the clinical and pathological differences between low-AFP-secreting (AFP < 20 ng/mL) and high-AFP-secreting (AFP ≥ 20 ng/mL) hepatocellular carcinomas in patients who undergo liver transplant (LT). MATERIAL AND METHODS We evaluated 145 patients who underwent deceased donor LT for HCC from January 1, 2005 until August 1, 2015 at the Johns Hopkins Hospital. RESULTS Median pre-LT AFP in the entire cohort was 13 ng/mL (IQR 6-59). Using serum AFP cutoff of 20 ng/mL, 61 (42%) patients had high-AFP-secreting tumors and 84 (58%) had low-AFP-secreting tumors. Patients with high-AFP-secreting tumors had larger lesions (3 cm vs. 2.4 cm, p = 0.024), and were more likely to have microvascular-invasion (36.1% vs. 20.2%, p = 0.02) and poor-differentiation (18% vs. 4.8%, p = 0.01), and tumor recurrence following LT (28% vs. 6%, p < 0.001). The 1-year, 3-year, and 5-year recurrence-free survival for patients in the low-AFP-secreting group compared to the high-AFP-secreting group were 100%, 92%, 92% vs. 81.3%, 71.3%, 68.5% respectively (p = 0.0003). CONCLUSION AFP is a suboptimal predictor of tumor recurrence following liver transplant in HCC patients. However, it can have some value in distinguishing more aggressive forms of HCC (high-AFP-secreting) that are associated with higher tumor recurrence. Novel tumor biomarkers are needed that can enhance predicting tumor recurrence following LT based on tumor biology.
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Affiliation(s)
- Ahmet Gurakar
- Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology-Transplant Hepatology, Baltimore, MD, United States.
| | - Michelle Ma
- Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology-Transplant Hepatology, Baltimore, MD, United States
| | - Jacqueline Garonzik-Wang
- Johns Hopkins University School of Medicine, Division of Transplant Surgery, Baltimore, MD, United States
| | - Amy Kim
- Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology-Transplant Hepatology, Baltimore, MD, United States
| | - Robert A Anders
- Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology-Transplant Hepatology, Baltimore, MD, United States
| | - Kiyoko Oshima
- Johns Hopkins University School of Medicine, Division of Pathology, Baltimore, MD, United States
| | - Christos Georgiades
- Johns Hopkins University School of Medicine, Division of Radiology, Baltimore, MD, United States
| | - Merve Gurakar
- Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, United States
| | - Shane Ottmann
- Johns Hopkins University School of Medicine, Division of Transplant Surgery, Baltimore, MD, United States
| | - Andrew M Cameron
- Johns Hopkins University School of Medicine, Division of Transplant Surgery, Baltimore, MD, United States
| | - Benjamin Philosophe
- Johns Hopkins University School of Medicine, Division of Transplant Surgery, Baltimore, MD, United States
| | - Behnam Saberi
- Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology-Transplant Hepatology, Baltimore, MD, United States
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Radtke A, Hennig F, Ikogho R, Hammel J, Anheuser P, Wülfing C, Belge G, Dieckmann KP. The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, Has a Very Rapid Decay in Patients with Clinical Stage 1. Urol Int 2018; 100:470-475. [PMID: 29698973 DOI: 10.1159/000488771] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 03/23/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Accumulating evidence suggests serum levels of microRNA (miR)-371a-3p to be a novel tumour marker of testicular germ cell tumours (GCTs). Presently, there is only limited information regarding the velocity of decline of serum levels in response to treatment. PATIENTS AND METHODS Twenty-four patients with testicular GCT (20 seminoma, 4 nonseminoma, median age 40 years) with clinical stage 1 had measurements of serum levels of miR-371a-3p preoperatively and repeatedly on the following 3 days. Three had additional tests done within 24 h after surgery. Measurement results were analysed using descriptive statistical methods. RESULTS Serum levels dropped to 2.62, 1.27, and 0.47% of the preoperative level within 1, 2, and 3 days, respectively. The computed half-life amounts to 3.7-7 h. The velocity of decay is significantly associated with tumour size. CONCLUSIONS Serum-levels of miR-371a-3p have a short half-life of less than 12 h. The rapid decay after treatment represents a valuable feature confirming the usefulness of miR-371a-3p as a valuable serum biomarker of GCT.
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Affiliation(s)
- Arlo Radtke
- Faculty of Biology and Chemistry, University of Bremen, Bremen, Germany
| | - Finja Hennig
- Faculty of Biology and Chemistry, University of Bremen, Bremen, Germany
| | - Raphael Ikogho
- Department of Urology, Albertinen Krankenhaus, Hamburg, Germany
| | - Johannes Hammel
- Department of Urology, Klinikum Bremen-Mitte, Bremen, Germany
| | - Petra Anheuser
- Department of Urology, Albertinen Krankenhaus, Hamburg, Germany.,Department of Urology, Asklepios Klinik St. Georg, Hamburg, Germany
| | - Christian Wülfing
- Department of Urology, Hodentumorzentrum Hamburg, Asklepios Klinik Altona, Hamburg, Germany
| | - Gazanfer Belge
- Faculty of Biology and Chemistry, University of Bremen, Bremen, Germany
| | - Klaus-Peter Dieckmann
- Department of Urology, Albertinen Krankenhaus, Hamburg, Germany.,Department of Urology, Hodentumorzentrum Hamburg, Asklepios Klinik Altona, Hamburg, Germany
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Denning C, Tay LJ, Carton J, Attar KH. Classical seminoma in a 92-year-old patient. World J Clin Urol 2017; 6:27-29. [DOI: 10.5410/wjcu.v6.i1.27] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Revised: 11/06/2016] [Accepted: 12/28/2016] [Indexed: 02/06/2023] Open
Abstract
Seminoma is a germ cell tumour which primarily affects the testes. Seminomas are treated by orchidectomy with usually excellent outcomes. We report the occurrence of a classical seminoma in a 92-year-old man, who is currently the oldest patient with this histology reported in literature. He presented with a painful, swollen testis. Scrotal ultrasound scan revealed a testicular mass. A left inguinal orchidectomy was carried out and histological examination confirmed the diagnosis of a classical seminoma. Further staging by computerised tomography revealed pulmonary lesions suspicious of metastases. The patient declined further treatment in view of his age and co-morbidities.
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Cebotaru CL, Olteanu ED, Antone NZ, Buiga R, Nagy V. Circulating tumor cells in germ cell tumors: are those biomarkers of real prognostic value? A review. ACTA ACUST UNITED AC 2016; 89:203-11. [PMID: 27152069 PMCID: PMC4849376 DOI: 10.15386/cjmed-570] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 09/22/2015] [Accepted: 10/03/2015] [Indexed: 12/14/2022]
Abstract
Analysis of circulating tumor cells from patients with different types of cancer is nowadays a fascinating new tool of research and their number is proven to be useful as a prognostic factor in metastatic breast, colon and prostate cancer patients. Studies are going beyond enumeration, exploring the circulating tumor cells to better understand the mechanisms of tumorigenesis, invasion and metastasis and their value for characterization, prognosis and tailoring of treatment. Few studies investigated the prognostic significance of circulating tumor cells in germ cell tumors. In this review, we examine the possible significance of the detection of circulating tumor cells in this setting.
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Affiliation(s)
- Cristina Ligia Cebotaru
- Ion Chiricuta Institute of Oncology, Cluj Napoca, Romania; Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | - Elena Diana Olteanu
- Ion Chiricuta Institute of Oncology, Cluj Napoca, Romania; Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
| | | | - Rares Buiga
- Ion Chiricuta Institute of Oncology, Cluj Napoca, Romania
| | - Viorica Nagy
- Ion Chiricuta Institute of Oncology, Cluj Napoca, Romania; Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
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7
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Dieckmann KP, Spiekermann M, Balks T, Ikogho R, Anheuser P, Wosniok W, Loening T, Bullerdiek J, Belge G. MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid. Urol Int 2016; 97:76-83. [DOI: 10.1159/000444303] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 01/27/2016] [Indexed: 12/21/2022]
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8
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Carver BS. Desperation Postchemotherapy Retroperitoneal Lymph Node Dissection for Metastatic Germ Cell Tumors. Urol Clin North Am 2015. [PMID: 26216821 DOI: 10.1016/j.ucl.2015.04.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Patients with persistently elevated serum tumor markers should be monitored for marker kinetics and evaluated for nonviable cancer causes of marker elevation. Desperation postchemotherapy retroperitoneal lymph node dissection is performed in select patients following second-line chemotherapy. Adjuvant postoperative chemotherapy is not indicated in patients following second-line chemotherapy.
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Affiliation(s)
- Brett S Carver
- Department of Surgery, Division of Urology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
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9
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MicroRNAs miR-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours. Br J Cancer 2012; 107:1754-60. [PMID: 23059743 PMCID: PMC3493876 DOI: 10.1038/bjc.2012.469] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND miRNAs are small noncoding RNA molecules that can be released into body fluids. Germ cell tumours (GCTs) overexpress miRNAs of the miR-371-3 cluster. Thus, serum levels of these miRNAs may correlate with tumour load. METHODS miRNAs of the miR-371-3 cluster were quantified in cubital vein blood samples of 20 GCT patients with clinical stage 1, and of 4 patients with advanced stages before and after treatment. In six patients testicular vein blood (TVB) was examined additionally. Seventeen healthy males served as controls. Likewise, expression of miRNAs in 15 matching tumour specimens was measured. RESULTS In all patients, serum levels of miRNAs 371-3 were much higher than in controls. In stage 1, levels decreased postoperatively 336.7-fold, 7.4-fold, and 7.7-fold for miRNAs 371a-3p, 372, and 373-3p, respectively (P<0.01). Also, in those cases with advanced disease levels dropped to the normal range after completion of treatment. miR-371-3 levels in TVB exceeded those in peripheral blood in all cases. Expression of miR-371a-3p was also documented in tumour tissue. However, no correlation was found regarding the extent of miRNA expression in tissue and the values measured in matching serum. CONCLUSION Thus, miR-371a-3p serum level appears to be a useful biomarker in GCTs.
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10
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Wani TA, Darwish IA. An automated flow immunosensor based on kinetic exclusion analysis for measurement of a free β-subunit of human chorionic gonadotropin in serum. NEW J CHEM 2012. [DOI: 10.1039/c2nj00003b] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Mohyudin MN, Arshad FA, Anand N. Horner's syndrome as a presenting sign of metastatic testicular malignancy. JRSM SHORT REPORTS 2011; 2:23. [PMID: 21541091 PMCID: PMC3086325 DOI: 10.1258/shorts.2011.010101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Mohamed N Mohyudin
- Department of Ophthalmology, Calderdale & Huddersfield NHS Trust, Huddersfield Royal Infirmary, Huddersfield, UK
| | - Faisal A Arshad
- Department of ENT, Head and Neck Surgery, Royal Hallamshire Hospital, Sheffield, UK
| | - Nitin Anand
- Department of Ophthalmology, Calderdale & Huddersfield NHS Trust, Huddersfield Royal Infirmary, Huddersfield, UK
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Kawaguchi T, Kumabe T, Kanamori M, Saito R, Yamashita Y, Sonoda Y, Watanabe M, Tominaga T. Logarithmic decrease of serum alpha-fetoprotein or human chorionic gonadotropin in response to chemotherapy can distinguish a subgroup with better prognosis among highly malignant intracranial non-germinomatous germ cell tumors. J Neurooncol 2011; 104:779-87. [DOI: 10.1007/s11060-011-0544-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2010] [Accepted: 02/15/2011] [Indexed: 01/28/2023]
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Arrieta O, Michel Ortega RM, Ángeles-Sánchez J, Villarreal-Garza C, Avilés-Salas A, Chanona-Vilchis JG, Aréchaga-Ocampo E, Luévano-González A, Jiménez MÁ, Aguilar JL. Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors. J Exp Clin Cancer Res 2009; 28:120. [PMID: 19709439 PMCID: PMC2745378 DOI: 10.1186/1756-9966-28-120] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2009] [Accepted: 08/27/2009] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors. METHODS We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP), and lactate dehydrogenase were measured prior to surgery. Vascular density (VD) and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis. RESULTS Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 +/- 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016), AFP > or = 14.7 ng/mL (p = 0.0001), and hCG > or = 25 mIU/mL (p = 0.0001). In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04). When hCG levels were stratified, concentrations > or = 25 mIU/mL were related with increased neovascularization (p < 0.0001). VEGF expression was not associated with VD or hCG serum levels. CONCLUSION This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.
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Affiliation(s)
- Oscar Arrieta
- Department of Medical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico
- Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico
- Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Rosa Mayela Michel Ortega
- Department of Medical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico
- Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico
| | | | - Cynthia Villarreal-Garza
- Universidad Nacional Autónoma de México, Mexico City, Mexico
- Department of Medical Oncology, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico
| | | | | | - Elena Aréchaga-Ocampo
- Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico
| | | | | | - José Luis Aguilar
- Department of Medical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico
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Hassan HC, Cullen IM, Casey RG, Rogers E. Gynaecomastia: an endocrine manifestation of testicular cancer. Andrologia 2008; 40:152-7. [DOI: 10.1111/j.1439-0272.2007.00815.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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15
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Clinical Significance of Low Level Human Chorionic Gonadotropin in the Management of Testicular Germ Cell Tumor. J Urol 2008; 179:930-4; discussion 934-5. [DOI: 10.1016/j.juro.2007.11.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Indexed: 11/18/2022]
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16
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Hassan R, Remaley AT, Sampson ML, Zhang J, Cox DD, Pingpank J, Alexander R, Willingham M, Pastan I, Onda M. Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer. Clin Cancer Res 2006; 12:447-53. [PMID: 16428485 DOI: 10.1158/1078-0432.ccr-05-1477] [Citation(s) in RCA: 203] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it. EXPERIMENTAL DESIGN We developed a sandwich ELISA using antibodies reacting with two different epitopes on human mesothelin. To quantitate serum mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56 patients with mesothelioma, and 21 patients with ovarian cancer were analyzed. Serum mesothelin levels were also measured before and after surgical cytoreduction in six patients with peritoneal mesothelioma. RESULTS Elevated serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were increased in 80% and 75% of the cases of mesothelioma and ovarian cancer, respectively, in which the tumors expressed mesothelin by immunohistochemistry. Out of the six patients with peritoneal mesothelioma who underwent surgery, four had elevated serum mesothelin levels before surgery. Out of these four patients, three had cytoreductive surgery and the serum mesothelin level decreased by 71% on postoperative day 1 and was undetectable by postoperative day 7. CONCLUSIONS We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.
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Affiliation(s)
- Raffit Hassan
- Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892, USA.
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Sanchez Yamamoto D, Hallquist Viale P, Roesser K, Lin A. The clinical use of tumor makers in select cancers: are you confident enough to discuss them with your patients? Oncol Nurs Forum 2005; 32:1013-22; quiz 1023-4. [PMID: 16136199 DOI: 10.1188/05.onf.1013-1025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE/OBJECTIVES To review the clinical use of tumor markers in select cancers and highlight future directions in tumor marker development. DATA SOURCES Guidelines from national and international societies, scientific literature, and Internet resources. DATA SYNTHESIS Tumor markers are important tools in the management of cancer. Sequencing of the human genome has led to new tumor marker development in the fields of proteomics and DNA microarray technologies. CONCLUSIONS Tumor marker technology is expanding rapidly; almost a dozen tumor markers currently are being used in the oncology arena, with many more in development. The use of tumor markers can be controversial, particularly because guidelines have not been established for all of the markers. IMPLICATIONS FOR NURSING Oncology nurses need to be well versed in the use of tumor markers to educate and counsel patients with cancer.
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Affiliation(s)
- Heinz-Josef Klümpen
- Department of Medical Oncology, F4-224, Academisch Centrum, Postbus 22660, 1100DD Amsterdam, Netherlands.
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Beck SDW, Patel MI, Sheinfeld J. Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors. J Urol 2004; 171:168-71. [PMID: 14665869 DOI: 10.1097/01.ju.0000099714.16082.78] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
PURPOSE Increased tumor markers after induction chemotherapy for patients with germ cell tumor usually represent systemic disease and consequently second line chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND) is reserved for patients with marker normalization. We report the concentration of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of post-chemotherapy cystic masses to evaluate this as a potential source for serum marker elevation. MATERIALS AND METHODS From March 2002 to December 2002, 11 consecutive patients with post-chemotherapy cystic masses underwent RPLND. Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post-chemotherapy RPLNDs were performed in patients with increased serum tumor markers, including the 3 patients in our study. Patients with increasing tumor markers and/or multifocal disease with noncystic residual masses after induction chemotherapy underwent salvage chemotherapy despite teratomatous elements in the primary tumor. RESULTS All 11 patients had teratoma in the orchiectomy specimen and retroperitoneum, including one with malignant transformation. Cystic fluid markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and 9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both serum markers normalized postoperatively. One patient with increased pre-RPLND serum HCG (11.6) had a cyst level of 233. HCG continued to increase postoperatively and the patient died of disease. The remaining 10 patients remain disease free. CONCLUSION Fluid from cystic teratoma contains variably elevated levels of HCG and AFP in all patients and appears to be independent of serum marker level or pathology. It is possible that a "slow leak" of fluid from cystic teratoma may explain elevated serum markers in selected patients with teratoma and thus may potentially avoid second line chemotherapy.
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Affiliation(s)
- Stephen D W Beck
- Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
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Albrecht W, Santis MD, Dossenbach-Glaninger A. Testicular tumor markers: Corner-stones in the management of malignant germ cell tumors / Hoden-Tumor-marker: Eckpfeiler in der Behandlung maligner Keimzelltumoren. ACTA ACUST UNITED AC 2004. [DOI: 10.1515/labmed.2004.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Tumor Markers. Surgery 2001. [DOI: 10.1007/978-3-642-57282-1_74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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22
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23
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Sturgeon CM, McAllister EJ. Analysis of hCG: clinical applications and assay requirements. Ann Clin Biochem 1998; 35 ( Pt 4):460-91. [PMID: 9681050 DOI: 10.1177/000456329803500402] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Study of the glycoprotein hormones, including hCG, is complex and evolving, and has benefited from recent major advances in analytical technology and molecular biology. It is important to be aware of the effect that these technological advances have, both on the analytical and the clinical requirements for provision of a diagnostic service for hCG. Some aspects of particular relevance are summarized in Table 10.
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Affiliation(s)
- C M Sturgeon
- Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, UK
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