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A Diagnostic Analysis Workflow to Optimal Multiple Tumor Markers to Predict the Nonmetastatic Breast Cancer from Breast Lumps. JOURNAL OF ONCOLOGY 2021; 2021:5579373. [PMID: 34335759 PMCID: PMC8289572 DOI: 10.1155/2021/5579373] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/30/2021] [Accepted: 06/28/2021] [Indexed: 12/24/2022]
Abstract
Objective To assess the diagnostic performance of clinically common single markers and combinations to distinguish nonmetastatic breast cancer and benign breast tumor. A predictive model with a better diagnostic ability for nonmetastatic breast cancer was established by using the diagnostic process. Methods A total of 222 patients with nonmetastatic breast cancer and 265 patients with benign breast disease were enrolled in this study. CEA, Ca 15-3, Ca 125, Ca 72-4, CYFRA 21-1, FERR, AFP, and NSE were measured by an electrochemiluminescent immunoenzymometric assay on the Elecsys system. There are four key steps for our diagnostic workflow, that is, feature selection, algorithm selection, parameter optimization, and outer test data was used to validate the optimal algorithm and markers. Results CEA, Ca 15-3, CYFRA 21-1, AFP, and FERR were selected using the t-test in our inner development set. The optimal algorithm among logical regression, decision tree, support vector machine, random forest, and gradient boost machine was selected by 10-fold cross-validation, and we found that random forest and logistic regression are the better classification. The outer test data was used to validate the best markers and classification. The random forest with CEA, Ca 15-3, CYFRA 21-1, AFP, and FERR showed the optimal combination for distinguishing breast cancer and benign breast disease. The AUC value was 0.888, the cut-off point was 0.484, and sensitivity and specificity were 78.9% and 90.1%. Conclusions No single marker of these eight markers was good at identifying nonmetastatic breast cancer from benign tumors. But a diagnostic analysis workflow was established to develop a predictive model with better diagnostic capability for nonmetastatic breast cancer. This workflow is also applicable to the optimization of other disease markers and diagnostic models. The predictive model showed good diagnostic performance, and it could be gradually incorporated as a support method for the diagnosis of nonmetastatic breast cancer.
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Lu J, Ding Y, Chen Y, Jiang J, Chen Y, Huang Y, Wu M, Li C, Kong M, Zhao W, Wang H, Zhang J, Li Z, Lu Y, Yu X, Jin K, Zhou D, Zhou T, Teng F, Zhang H, Zhou Z, Wang H, Teng L. Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets. Nat Commun 2021; 12:3946. [PMID: 34168152 PMCID: PMC8225795 DOI: 10.1038/s41467-021-24170-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 06/01/2021] [Indexed: 02/05/2023] Open
Abstract
Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer. However, little is known about the genomic features of this disease. We perform whole-exome sequencing analysis of AFPGC, and identify 34 significantly mutated genes. Somatic copy number alterations analysis reveals several significant focal amplifications (e.g. 19q12, 17q12) and focal deletions (e.g. 1p36.11, 9p21.3), and some of these negatively affect the patient prognosis. Comparative analyses reveal that AFPGC has distinct genomic features from gastric cancer of The Cancer Genome Atlas as well as four molecular subtypes. Several frequently altered genes with potential as therapeutic targets are identified in AFPGC. Further analysis reveals that AFPGC with amplification of CCNE1 at 19q12 and/or ERBB2 at 17q12 show poorer survival and more aggressive. Subsequently, based on our established patient-derived xenograft models for AFPGC, translational research is performed and the therapeutic value of targeting CCNE1 and ERBB2 is validated. In this work, we provide an understanding of genomic characteristics of AFPGC and propose a platform to explore and validate the genome-guided personalized treatment for this disease.
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Affiliation(s)
- Jun Lu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yongfeng Ding
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Junjie Jiang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yingying Huang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Mengjie Wu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chengzhi Li
- Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Mei Kong
- Department of Pathology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wenyi Zhao
- Innovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Zhejiang University, Hangzhou, China
| | - Haohao Wang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Zhang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhongqi Li
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yimin Lu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiongfei Yu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ketao Jin
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Donghui Zhou
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tianhua Zhou
- Institute of Gastroenterology, Cancer center, Zhejiang University, Hangzhou, China
| | - Fei Teng
- Hangzhou Oncocare Co. Ltd, Hangzhou, China
| | - Haibin Zhang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhan Zhou
- Innovation Institute for Artificial Intelligence in Medicine and Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences and Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Zhejiang University, Hangzhou, China.
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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Ma R, Zhao Y, He M, Zhao H, Zhang Y, Zhou S, Gao M, Di D, Wang J, Ding J, Wei M. Identifying a ten-microRNA signature as a superior prognosis biomarker in colon adenocarcinoma. Cancer Cell Int 2019; 19:360. [PMID: 31892859 PMCID: PMC6937800 DOI: 10.1186/s12935-019-1074-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 12/13/2019] [Indexed: 12/16/2022] Open
Abstract
Background Increasing studies have suggested that aberrant expression of microRNAs might play essential roles in the progression of cancers. In this study, we sought to construct a high-specific and superior microRNAs signature to improve the survival prediction of colon adenocarcinoma (COAD) patients. Methods The genome-wide miRNAs, mRNA and lncRNA expression profiles and corresponding clinical information of COAD were collected from the TCGA database. Differential expression analysis, Kaplan–Meier curve and time-dependent ROC curve were calculated and performed using R software and GraphPad Prism7. Univariate and multivariate Cox analysis was performed to evaluate the prognostic ability of signature. Functional enrichment analysis was analyzed using STRING database. Results We identified ten prognosis-related microRNAs, including seven risky factors (hsa-miR-197, hsa-miR-32, hsa-miR-887, hsa-miR-3199-2, hsa-miR-4999, hsa-miR-561, hsa-miR-210) and three protective factors (hsa-miR-3917, hsa-miR-3189, hsa-miR-6854). The Kaplan–Meier survival analysis showed that the patients with high risk score had shorter overall survival (OS) in test series. And the similar results were observed in both validation and entire series. The time-dependent ROC curve suggested this signature have high accuracy of OS for COAD. The Multivariate Cox regression analysis and stratification analysis suggested that the ten-microRNA signature was an independent factor after being adjusted with other clinical characteristics. In addition, we also found microRNA signature have higher AUC than other signature. Furthermore, we identified some miRNA-target genes that affect lymphatic metastasis and invasion of COAD patients. Conclusion In this study, we established a ten-microRNA signature as a potentially reliable and independent biomarker for survival prediction of COAD patients.
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Affiliation(s)
- Rong Ma
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Yanyun Zhao
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Miao He
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Hongliang Zhao
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Yifan Zhang
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Shuqi Zhou
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Mengcong Gao
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Di Di
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Jue Wang
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
| | - Jian Ding
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,3Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Minjie Wei
- 1Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning China.,2Liaoning Engineering Technology Research Center, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122 Liaoning People's Republic of China
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Chen EB, Wei YC, Liu HN, Tang C, Liu ML, Peng K, Liu T. Hepatoid Adenocarcinoma of Stomach: Emphasis on the Clinical Relationship with Alpha-Fetoprotein-Positive Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2019; 2019:6710428. [PMID: 31915699 PMCID: PMC6930719 DOI: 10.1155/2019/6710428] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 11/25/2019] [Indexed: 12/13/2022]
Abstract
AIMS Both hepatoid adenocarcinoma of stomach (HAS) and alpha-fetoprotein-positive gastric cancer (AFPGC) are rare but aggressive subtypes of gastric cancer, but few studies focus on the clinicopathologic differences and prognostic factors between them because of their rarity and histologic overlap. And the significance of AFP level in HAS prognosis was not well studied. METHODS 41 patients with AFPGC and 52 patients with HAS were included in this study. The clinicopathologic features were compared by Chi-square analysis. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analyzed with the Kaplan-Meier method. RESULTS The patients with HAS were of a younger age compared with AFPGC, and nearly 60% of tumor located in the gastric antrum and the gastric fundus of cardia. The OS of AFPGC was shorter than that of HAS, due to a higher rate of metastasis. Furthermore, the survival analysis showed that HAS with high AFP expression (AFPHigh HAS) had a significantly poorer OS compared to HAS with low AFP expression (AFPLow HAS) (P=0.046). CONCLUSIONS Compared with AFPGC, the patients of HAS were of a younger age and had less rate of liver and other organ metastasis. The serum AFP level was a sensitive prognostic indicator for OS. Therefore, much attention should be paid to AFPHigh HAS in clinical practice.
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Affiliation(s)
- Er-Bao Chen
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi-Chou Wei
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hai-Ning Liu
- Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Cheng Tang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Meng-Ling Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ke Peng
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
- Center of Evidence-Based Medicine, Fudan University, Shanghai, China
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He Y, Lu H, Zhang L. Serum AFP levels in patients suffering from 47 different types of cancers and noncancer diseases. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2019; 162:199-212. [PMID: 30905450 DOI: 10.1016/bs.pmbts.2019.01.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Alpha-fetoprotein (AFP) is a glycoprotein and belongs to the gene family of serum albumins. The serum AFP levels were found to be elevated in the sera of liver cancer patients in 1964 and were subsequently developed and used as a liver cancer biomarker. However, elevated serum AFP levels have been observed in patients suffering from other cancer and noncancer diseases. Up to date, a systematic comparison of the serum AFP levels in different diseases has not been reported. In current study, 66,682 clinical lab test results of serum AFP levels from healthy individuals and patients with 47 different types of diseases during the past 5 years were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering from liver, breast, esophagus, cervical, pancreatic, endometrial, gastric, lung, rectum cancers in addition to noncancer diseases cirrhosis, nephrotic syndrome, and gastritis had significantly (p<0.05) increased, whereas patients suffering from multiple myeloma, Wilms' tumor, and other 22 types of noncancer diseases had significantly decreased median serum AFP levels than that of healthy controls. Moreover, patients with liver cancer, cirrhosis, lymphoma, bone fracture, and Wilms' tumor had highest mean serum AFP levels and the biggest SD values. In summary, the increased serum AFP levels were most evident but not specific for liver cancer patients. The potential clinical use of the increased or decreased serum AFP levels for other types of cancer and noncancer diseases and the molecular mechanisms behind our current findings need to be investigated.
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Affiliation(s)
- Yanli He
- Systems Biology and Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China.
| | - Haijun Lu
- Department of Radiology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lijuan Zhang
- Systems Biology and Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China.
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Buraggi GL, Bombardieri E, Castellani MR, Rodari A, Crippa F. Association of Cea Test and Liver Scan in Detection of Hepatic Metastases of Gastrointestinal Carcinoma. TUMORI JOURNAL 2018; 67:553-8. [PMID: 7336482 DOI: 10.1177/030089168106700607] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The authors evaluate the combined use of liver scan and the CEA test in the diagnosis of hepatic metastases of carcinoma of the gastrointestinal tract. Association of the two tests is justified by the fact that the liver scan is very specific but not very sensitive, whereas the CEA test is more sensitive and not very specific. The sensitivity of the CEA test, on the other hand, can be increased by increasing the threshold of normality. However, the associated diagnostic use of the liver scan and the CEA test gives a loss of specificity with respect to the use of the liver scan alone. The present study, carried out on a series of 376 patients affected by gastrointestinal tumors of which 79 were of the stomach (9 with hepatic metastases), 133 of the colon and higher sigmoid (25 with hepatic metastases), and 164 of the lower sigmoid and rectum (29 with hepatic metastases), proposed to establish by use of a statistical method the optimal threshold of the CEA test that would give the best diagnostic specificity of the combined CEA test and liver scan without any relevant loss of sensitivity. A threshold of 26 ng/ml of the CEA test gave a specificity of 92 %, a sensitivity of 80 %, and an accuracy of 90 %. The authors think that in the detection of liver metastases of gastrointestinal tumors, the combined test can be more helpful the less the probability, for a given patient, for other metastatic localizations.
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Multimodality Treatment Including Triplet Regimen as First-Line Chemotherapy May Improve Prognosis of Serum AFP-Elevated Gastric Cancer with Liver Metastasis. Gastroenterol Res Pract 2018; 2017:5080361. [PMID: 29434637 PMCID: PMC5757133 DOI: 10.1155/2017/5080361] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 11/27/2017] [Indexed: 12/20/2022] Open
Abstract
Serum α-fetoprotein- (AFP-) elevated gastric cancer is a rare tumor that has a poor prognosis due to high incidence of liver metastasis. This study sought to investigate the optimal treatment modality. A total of 319 gastric cancer patients with liver metastasis (GCLM) whose serum AFP levels were tested before treatment were enrolled in this study. They were classified as the serum AFP ≥ 20 ng/ml group (n = 74) and the AFP < 20 ng/ml group (n = 245). Median OS of the AFP < 20 ng/ml group was significantly longer than that of the AFP ≥ 20 ng/ml group (15.7 m versus 10.9 m, P = 0.004). ORR of first-line chemotherapy was 43.3% and 56.1% of the two groups, respectively (P = 0.024). Of patients who received doublet regimen, ORR of the AFP ≥ 20 ng/ml group was significantly lower (38.2 versus 56.9%, P = 0.013), while in those received triplet regimens, ORR between two groups was similar (66.7% versus 66.7%, P = 0.676). Moreover, for patients of the AFP ≥ 20 ng/ml group, those who reached PR had a longer survival period (15.4 m versus 9.4 m, P = 0.017), and combined with local treatment for liver metastasis also seemed to improve prognosis (19.2 m versus 8.4 m, P = 0.003). In conclusion, serum AFP-elevated GCLM had a poorer prognosis. Multimodality treatment including aggressive first-line chemotherapy with triplet regimen may be needed when treating them.
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Wang YK, Shen L, Jiao X, Zhang XT. Predictive and prognostic value of serum AFP level and its dynamic changes in advanced gastric cancer patients with elevated serum AFP. World J Gastroenterol 2018; 24:266-273. [PMID: 29375212 PMCID: PMC5768945 DOI: 10.3748/wjg.v24.i2.266] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 11/18/2017] [Accepted: 12/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate predictive and prognostic value of serum alpha-fetoprotein (AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP (AFPAGC).
METHODS One hundred and five patients with AFPAGC were enrolled in the study, and all of them underwent at least one cycle of systemic chemotherapy at our institute and had serum AFP ≥ 20 ng/mL at diagnosis or recurrence. Clinicopathologic features, serum AFP level at diagnosis and changes during treatment, first-line chemotherapy regimens, efficacy and toxicity, and survival information were collected. A Person’s χ2 or Fisher’s exact test was used to measure the differences between variables. Survival prognostic factors were investigated using the Kaplan-Meier method and Cox regression.
RESULTS Median serum AFP level was 161.7 ng/mL (range, 22.9-2557110 ng/mL). Objective response rates (ORR) was significantly lower in the AFP ≥ 160 ng/mL group than in the AFP < 160 ng/mL group (30.4% vs 68.3%, P < 0.001). ORR to doublet regimens was significantly lower in the AFP ≥ 160 ng/mL group, whereas ORR to triplet regimens was similar between the two groups. Liver metastasis rate was significantly higher in the AFP ≥ 160 ng/mL group than in the AFP < 160 ng/mL (69.8% vs 50.0%, P < 0.001). Overall survival (OS) in the two cohorts did not show any significant difference (P = 0.712). Dynamic changes of AFP were consistent with response to chemotherapy, and median OS of patients with a serum AFP decline ≥ 50% and those with a serum AFP decline < 50% was 17.5 m and 10.0 m, respectively (P = 0.003). Hepatic (P = 0.005), peritoneal (P < 0.001), non-regional lymph node metastasis (P < 0.001), and portal vein tumor thrombus (PVTT) (P = 0.042) were identified as independent prognostic factors for AFPAGC.
CONCLUSION Real-time examination of AFP has great predictive and prognostic value for managing AFPAGC. For those with markedly elevated AFP, triplet regimens may be a better choice.
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Affiliation(s)
- Ya-Kun Wang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xi Jiao
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiao-Tian Zhang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China
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McMurray W. Primary Hepatoma Presenting with Central Abdominal Pain and Diagnosed from a Raised Serum Alpha-Fetoprotein Level. Proc R Soc Med 2016. [DOI: 10.1177/003591577306600946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- William McMurray
- Chemical Pathology Department, University College Hospital, Gower Street, London WClE6AU
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Li XD, Wu CP, Ji M, Wu J, Lu B, Shi HB, Jiang JT. Characteristic analysis of α-fetoprotein-producing gastric carcinoma in China. World J Surg Oncol 2013; 11:246. [PMID: 24083471 PMCID: PMC3849988 DOI: 10.1186/1477-7819-11-246] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 09/22/2013] [Indexed: 12/16/2022] Open
Abstract
α-Fetoprotein-producing gastric cancer (AFPGC) is a rare type of gastric cancer. The largest population of patients with AFPGC is found in China. In the present study, a total of 4,779 GC patients, including 317 AFPGC patients, from 11 clinical studies in China with a general AFPGC/GC ratio of 6.63% were summarized and analyzed. On the basis of analysis of the clinical data, the patients with AFPGC had larger tumor size, weaker cell differentiation, worse histopathological types, deeper serosal infiltration, more lymph node and liver metastases, poorer stages, shorter survival time and more positive expression of vascular endothelial growth factors than the patients without AFPGC. Our observation is consistent with previous results reported in studies of AFPGC. Overall, AFPGC is a subtype of GC with a poor prognosis.
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Affiliation(s)
- Xiao-Dong Li
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, Jiangsu Province, People's Republic of China.
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Tsuchiya A, Kanefuji T, Suda T, Aoyagi T, Osaki A, Togashi T, Kawauchi Y, Fushiki M, Watanabe G, Hirota M, Nomoto M, Ajioka Y, Aoyagi Y. Alpha-fetoprotein-producing adenocarcinoma in which the metastatic route was determined from calcified lesions. Clin J Gastroenterol 2011; 4:89-94. [PMID: 26190712 DOI: 10.1007/s12328-011-0209-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2010] [Accepted: 01/24/2011] [Indexed: 02/07/2023]
Abstract
Alpha-fetoprotein (AFP)-producing adenocarcinoma is known for its rapid progression and poor prognosis, and chemotherapy regimens are yet to be standardized. Here we describe the first report of AFP-producing adenocarcinoma with calcification. The metastatic route was visualized from the calcification, and combination chemotherapy was performed. A 77-year-old Japanese man was transferred to our hospital for treatment of liver tumors. Computed tomography (CT) revealed multiple liver tumors with portal vein tumor thrombosis. The tumors were highly attenuated before enhancement, suggesting various degrees of calcification. Serum levels of carcinoembryonic antigen (CEA), AFP, and the proportion of fucosylated AFP were considerably elevated. Gastroduodenoscopy revealed an elevated tumor occupying the duodenal bulb with an ulcerative lesion in the vicinity of the gastroduodenal junction, and biopsy specimens from the duodenum and liver revealed medullary adenocarcinoma with calcification. Three-dimensional reconstruction of CT images clearly showed that the calcified lesions had spread from the gastroduodenal junction to the liver via a route comprising the corresponding local vein, the superior mesenteric vein, and portal vein. The patient was accordingly diagnosed with calcified AFP-producing adenocarcinoma with multiple liver metastases. Combination chemotherapy using TS-1 and cisplatin (CDDP) resulted in a striking response for the initial 4 months in terms of tumor markers and CT findings. This is the first report of AFP-producing adenocarcinoma with calcification. A metastatic route from the primary tumor to the liver was clearly visualized by tracing the calcified lesions. Combination chemotherapy based on 5-fluorouracil and CDDP may have the potential to prolong survival.
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Affiliation(s)
- Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan.
| | - Tsutomu Kanefuji
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Takeshi Suda
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Tomoya Aoyagi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Akihiko Osaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Tadayuki Togashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Yusuke Kawauchi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Mae Fushiki
- Division of Molecular Diagnostic Pathology, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Gen Watanabe
- Division of Molecular Diagnostic Pathology, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Masaki Hirota
- Department of Surgery, Niigata Prefecture Muikamachi Hospital, Minamiuonuma, Japan
| | - Minoru Nomoto
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Yoichi Ajioka
- Division of Molecular Diagnostic Pathology, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Yutaka Aoyagi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-Dori, Chuo-ku, Niigata, 951-8510, Japan
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Takeyama H, Sawai H, Wakasugi T, Takahashi H, Matsuo Y, Ochi N, Yasuda A, Sato M, Okada Y, Funahashi H, Akamo Y, Manabe T. Successful paclitaxel-based chemotherapy for an alpha-fetoprotein-producing gastric cancer patient with multiple liver metastases. World J Surg Oncol 2007; 5:79. [PMID: 17634124 PMCID: PMC1939849 DOI: 10.1186/1477-7819-5-79] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2007] [Accepted: 07/16/2007] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Alpha-fetoprotein (AFP)-producing gastric cancer is known to frequently cause multiple liver metastases and to have an extremely poor prognosis. CASE PRESENTATION A 64-year-old Japanese man admitted to our hospital was diagnosed with gastric cancer with liver metastases. He underwent a total gastrectomy with splenectomy, and pathological stage IV disease according to the classification proposed by the Japanese Gastric Cancer Association was assigned. The histological diagnosis was poorly differentiated adenocarcinoma, and tumor production of AFP was confirmed by immunohistochemical staining. Following surgery, the patient received combination chemotherapy consisting of TS-1 and paclitaxel. Initially, AFP levels decreased dramatically and computed tomography (CT) revealed regression of liver metastases. However, multiple new liver metastases appeared and serum AFP levels increased after 5 months. A regimen of 5-FU plus paclitaxel followed by paclitaxel monotherapy was used next. Serum AFP levels once again decreased and CT showed regression or disappearance of liver metastases. The patient currently has a very good quality of life, and is receiving weekly paclitaxel monotherapy as an outpatient. No progression of liver metastases has been observed to date. CONCLUSION We consider this rare case to have significant value with respect to treatment of AFP-producing gastric cancer with multiple liver metastases, and propose that combining surgery with chemotherapeutic agents such as paclitaxel may lead to a better prognosis in such cases.
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Affiliation(s)
- Hiromitsu Takeyama
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Hirozumi Sawai
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Takehiro Wakasugi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Hiroki Takahashi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Yoichi Matsuo
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Nobuo Ochi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Akira Yasuda
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Mikinori Sato
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Yuji Okada
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Hitoshi Funahashi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Yoshimi Akamo
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
| | - Tadao Manabe
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan
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13
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Kurihara K, Konishi F, Kanazawa K, Fujii T, Saito K. Alpha-fetoprotein-producing carcinoma of the colon: report of a case. Surg Today 1997; 27:453-6. [PMID: 9130351 DOI: 10.1007/bf02385712] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We report herein the rare case of a 67-year-old man in whom alpha-feto-protein (AFP)-producing carcinoma originated in the transverse colon, describing the clinical course of the patient and the histological features of the tumor. At the age of 63, the patient had been diagnosed as having sigmoid colon carcinoma, and surgery was carried out. However, 4 years later, his fecal occult blood test was positive, and further investigation revealed a transverse colon carcinoma with liver metastasis. The serum AFP measured preoperatively was 10978 ng/ml. Resection of the transverse colon and a liver biopsy were performed, following which his serum AFP level decreased to 4804 ng/ml. Histology of the ulcerated lesion in the transverse colon showed a poorly differentiated adenocarcinoma with a medullary growth pattern. Using an immunohistochemical staining method, AFP-producing cells were detected in the transverse colon carcinoma and the liver metastasis. Based on our experience of this patient and a review of the literature on the few cases previously reported, we conclude that AFP-producing coloretal carcinoma has a tendency to produce blood-borne metastasis and to be associated with a poor prognosis.
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Affiliation(s)
- K Kurihara
- Department of Surgery, Jichi Medical School, Tochigi, Japan
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14
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Abstract
BACKGROUND Alpha-fetoprotein (AFP) is a useful tumor marker for hepatoma and yolk sac tumor. Recently, elevations of serum AFP were reported in patients with other malignancies, especially gastric cancers. Two distinct tumor morphologies, hepatoid and clear cell, have been correlated with AFP production. METHODS Two patients with AFP-producing gastric carcinoma were evaluated with immunohistochemical, ultrastructural, and biochemical studies. RESULTS In Patient 1, the primary and metastatic carcinomas consisted homogeneously of tubulopapillary carcinoma with clear cytoplasm. In Patient 2, the cancer was composed of three different areas: tubulopapillary carcinoma with clear cytoplasm, tumor cartilage, and so-called hepatoid carcinoma. The morphologic characteristics of tubulopapillary carcinoma with clear cytoplasm were similar to those of the developing gut epithelium at the stage of 2-4 months' gestation. The elution patterns of the serum AFP on lectin-affinity sepharose column study also suggested a correlation with fetal gut differentiation. CONCLUSIONS AFP-producing clear cell gastric carcinomas are differentiated into fetal intestine. One patient also had hepatocytic and cartilaginous differentiation, indicative of a blastomatous characteristic of the tumor. These tumors arose in association with intestinal metaplasia.
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Affiliation(s)
- H Matsunou
- Department of Pathology, Kanazawa Medical University, Ishikawa-ken, Japan
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15
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Abstract
BACKGROUND The clinicopathologic and immunohistochemical features of the primary gastric hepatoid adenocarcinomas still remain unclear. METHODS The authors evaluated 28 hepatoid adenocarcinomas (HC) of the stomach on the basis of characteristic histologic features resembling hepatocellular carcinoma, which were selected from the 7200 cases of primary gastric carcinoma in their files. Additionally, 22 alpha-fetoprotein (AFP)-positive adenocarcinomas without hepatoid features (APC) were also selected. RESULTS The HC cases fell into the following two groups: HC with AFP-positive tumor cells (Group 1; 15 cases) and HC without AFP-positive cells (Group 2; 13 cases). Histologically, the glycogen granules and hyaline globules were common features in HC. The incidence of a venous invasion of HC (Groups 1 and 2) was higher than that of APC (Group 3). There were no significant differences among the three groups regarding clinical features, macroscopic features, and the incidence of lymphatic permeation. An immunohistochemical study showed that HC had differentiation into various directions. As for the advanced carcinomas, the 5-year survival rates of patients with HC (Groups 1 and 2) and those with APC (Group 3) were 11.9% (21.4%, 8.3%) and 38.2%, respectively. The prognosis of Group 1 was similar to that of Group 2, but was poorer than that of Group 3. CONCLUSIONS The findings suggested that HC, as shown by its characteristic histologic features, had a poor prognosis whether producing AFP or not, and that HC should therefore be distinguished from AFP-positive carcinoma without hepatoid features.
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Affiliation(s)
- E Nagai
- Second Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
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16
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Aoyagi Y, Suzuki Y, Igarashi K, Saitoh A, Oguro M, Yokota T, Mori S, Suda T, Isemura M, Asakura H. Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans. Br J Cancer 1993; 67:486-492. [PMID: 7679920 PMCID: PMC1968279 DOI: 10.1038/bjc.1993.91] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Chemical structures of the sugar chains of various human alpha-fetoprotein (AFP) species with different affinity for Concanavalin A (Con A) and Lens culinaris agglutinin (LCA) were examined by pyridylamination of their oligosaccharides and stepwise exoglycosidase digestion. Using reversed-phase and size-fractionation high performance liquid chromatography systems we identified six pyridylamino-sugar chains. The Con A-reactive and LCA-nonreactive species of AFP from patients with hepatocellular carcinoma contained a biantennary sugar chain, and the Con A-reactive and LCA-reactive species had a biantennary one with a fucose residue at the innermost N-acetylglucosamine residue. The Con A-nonreactive and LCA-reactive species contained a biantennary sugar chain both with a bisecting-N-acetylglucosamine residue at the trimannosyl core and with a focus residue at the innermost N-acetylglucosamine residue. The Con A-nonreactive and LCA-nonreactive species contained a fucosylated triantennary sugar chain as a major component, and two minor components: a triantennary sugar chain and a biantennary sugar chain with a bisecting-N-acetylglucosamine residue at the trimannosyl core. Thus, the fucosylated and non-fucosylated triantennary sugar chains were newly identified in human AFP. Essentially identical results were obtained for AFP from the patient with gallbladder carcinoma which metastasizes to the liver. These results indicate that the increment in fucosylation and branching to form new antennae is a characteristic feature of the carbohydrate chains of AFP from patients with neoplastic diseases of the liver.
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Affiliation(s)
- Y Aoyagi
- Department of Internal Medicine, Niigata University School of Medicine, Japan
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17
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Aoyagi Y, Suzuki Y, Igarashi K, Saitoh A, Oguro M, Yokota T, Mori S, Nomoto M, Isemura M, Asakura H. The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver. Cancer 1991; 67:2390-4. [PMID: 1707341 DOI: 10.1002/1097-0142(19910501)67:9<2390::aid-cncr2820670928>3.0.co;2-v] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver.
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Affiliation(s)
- Y Aoyagi
- Department of Internal Medicine, Niigata University School of Medicine, Japan
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18
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Borchard F. Letter to the case. Pathol Res Pract 1989. [DOI: 10.1016/s0344-0338(89)80024-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Hamazoe R, Yoshioka H, Ikeda Y, Shimizu N, Koga S. Alpha-fetoprotein-producing pancreatic carcinoma: case report and review of the Japanese literature. GASTROENTEROLOGIA JAPONICA 1987; 22:503-8. [PMID: 2444486 DOI: 10.1007/bf02773820] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
An autopsy was performed of a patient who succumbed to pancreatic carcinoma and in whom an unusually high level of serum alpha-fetoprotein (AFP) (84,000 ng/ml) was obtained. An immunohistochemical approach, utilizing the peroxidase-antiperoxidase method, proved that AFP was confined within pancreatic carcinomatous cells of the primary lesion and liver metastases. No AFP-positive cells were ever observed in the hepatocytes adjacent to the metastatic lesions in the liver. It may be inferred that, in this particular case, the carcinomatous cells themselves synthesize AFP. The sites of production of AFP in AFP-positive pancreatic carcinoma were discussed in a review of the literature.
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Affiliation(s)
- R Hamazoe
- First Department of Surgery, Tottori University School of Medicine, Yonago, Japan
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20
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Koyama S, Ebihara T, Osuga T. Histologic and immunohistochemical studies of alpha-fetoprotein (AFP)-producing gastric carcinoma. GASTROENTEROLOGIA JAPONICA 1987; 22:419-27. [PMID: 2444485 DOI: 10.1007/bf02773808] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Five gastric adenocarcinomas and their metastatic nodules in the liver with high serum AFP levels were examined by histologic and immunohistochemical methods. The examination revealed that AFP-producing stomach cancers were poorly differentiated carcinoma cells, especially with medullary arrangements, or pleomorphic or multinucleated giant cells. Well-differentiated papillotubular adenocarcinoma tissues on the glandular epithelium were not stained with anti-AFP. One out of the five AFP-producing adenocarcinomas with medullary patterns resembled liver cell carcinoma on light microscopy. However, an ultrastructural study showed tumor cells of the intestinal type, since the cells possessed a ductal lumina with abundant microvilli and a secretory granules. The findings suggest that the tumor cells differentiated in an intestinal direction rather than hepatic direction. In addition, we noted three simultaneously CEA-positive cases out of five AFP-producing gastric carcinomas. CEA was strongly stained in well differentiated adenocarcinoma tissues in the glandular epithelium or in areas of medullary type carcinoma invasion. However, CEA was not detected in undifferentiated carcinoma cells.
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Affiliation(s)
- S Koyama
- Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan
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21
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Motoyama T, Saito K, Iwafuchi M, Watanabe H. Endodermal sinus tumor of the stomach. ACTA PATHOLOGICA JAPONICA 1985; 35:497-505. [PMID: 2411108 DOI: 10.1111/j.1440-1827.1985.tb00592.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
This is a case report of an endodermal sinus tumor arising in the stomach of a 72-year-old Japanese woman. The tumor showed Borrmann 2 type at the mucosal surface, and the main mass occupied the subserosal layer with outgoing extension. Microscopically, the tumor showed typical characteristics of the endodermal sinus tumor, associated with embryonal carcinoma, poorly differentiated adenocarcinoma and well differentiated tubular adenocarcinoma. Alpha-fetoprotein was detected in the serum of the patient by radioimmunoassay and within tumor tissue by immunohistochemical techniques. Ultrastructurally, a characteristic basement membrane-like material has been identified in intercellular spaces.
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22
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Zumla A, Voller A. A serological study on primary hepatocellular carcinoma in Zambia. Trans R Soc Trop Med Hyg 1982; 76:546-51. [PMID: 6190277 DOI: 10.1016/0035-9203(82)90160-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
The enzyme linked immunosorbent assay (ELISA) was used to measure alpha-foetoprotein (AFP) levels and to detect Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B surface antigen (anti-HBs) in patients with primary hepatocellular carcinoma and in controls free of the disease in Zambia. Virtually all the patients with primary hepatocellular carcinoma had grossly elevated AFP levels and about two thirds of them were positive for HBsAg. All the controls had much lower AFP levels and one sixth were positive for HBsAg.
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23
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Kodama T, Kameya T, Hirota T, Shimosato Y, Ohkura H, Mukojima T, Kitaoka H. Production of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: histologic and immunohistochemical analyses of 35 cases. Cancer 1981; 48:1647-55. [PMID: 6169423 DOI: 10.1002/1097-0142(19811001)48:7<1647::aid-cncr2820480729>3.0.co;2-v] [Citation(s) in RCA: 115] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
By immunoperoxidase histochemical staining of formalin-fixed paraffin-embedded sections, the production of alpha-fetoprotein(AFP), albumin(ALB), transferrin(TF), alpha-1-antitrypsin(AAT), and human chorionic gonadotropin(HCG) was examined in 35 operatively resected stomach cancers with elevated serum AFP levels (higher than 20 ng/ml as determined by radioimmunoassay). Cells positive for AFP were found in 19 cases (54%). In 29 cases (83%), some tumor cells contained normal serum proteins (ALB, TF, or AAT). All 19 tumors with AFP-positive cells also stained positively for two or three kinds of normal serum proteins. In some cases, AFP and normal serum proteins were localized in the same cells. There were two cases in which metastatic tumors produced AFP, whereas the primary sites did not. In nine cases (26%), HCG was present in tumor cells and HCG- and AFP-positive cells were coexistent in six tumors. Histologic examination of AFP-producing stomach tumors revealed medullary or papillotubular arrangements with marked nuclear atypia and eosinophilic granular or clear cytoplasms containing no glycogen or mucin. Some tumors with medullary patterns resembled liver cell carcinomas. Concordant phenotypic expression of AFP and normal serum protein production appears to be a general feature of AFP-producing tumors such as liver cell carcinoma, yolk sac tumor, and stomach cancer.
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Abstract
A case of primary lung cancer that produced both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) is presented. Alphafetoprotein in the supernatant of tissue extract from the primary lesion amounted to more than 40 microgram/ml, and its exact origin from tumor tissues was confirmed by the immunofluorescent study. We suppose that since the lung is one of the foregut derivatives it is not unlikely for lung cancer cells to produce AFP as well as CEA.
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26
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Aburano T, Tonami N, Tada A, Hisada K. Radioimmunoassay for carcinoembryonic antigen and alpha 1-fetoprotein in the qualitative evaluation of focal hepatic lesions in Japan. EUROPEAN JOURNAL OF NUCLEAR MEDICINE 1980; 5:373-6. [PMID: 6156837 DOI: 10.1007/bf00445625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The combined tests of serum alpha 1-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were routinely performed in 210 patients with focal hepatic lesions on a 99mTc-colloid liver scan in order to determine whether these could provide more useful information that AFP test alone in the qualitative evaluation of focal hepatic lesions. The predictive value of hepatoma with positive AFP alone remained 80%. However, when the negative CEA was combined with positive AFP, the predictive value of hepatoma (91%) with both was greatly increased. On the other hand, the predictive value of metastatic liver cancer with positive CEA showed 92%. The combined test of AFP and CEA may be useful for preserving high predictive values of hepatoma and metastatic liver disease.
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27
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Mori H, Onji M, Yoshida A, Fukunishi R. Serum alpha-fetoprotein-positive gastric carcinoid with liver metastasis. VIRCHOWS ARCHIV. A, PATHOLOGICAL ANATOMY AND HISTOLOGY 1980; 387:107-16. [PMID: 6162267 DOI: 10.1007/bf00428433] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The patient was a 60-year-old Japanese male. He complained of epigastralgia and right chest pain of 4 month's duration, and general malaise, nausea and vomiting of 2 month's duration. Physical examination revealed on the right third rib a tender mass with a diameter of 2 cm and hepatomegaly with a multi-nodular surface and red palms. There were no signs of carcinoid syndrome, such as cutaneous flushing. Laboratory examinations disclosed certain biochemical alterations; alkaline phosphatase 810 IU/l, gamma-glutamyl transpeptidase (gamma-GTP) 2090 IU/l, carcinoembryonic antigen (CEA) 23.5 ng/ml and alpha-fetoprotein (AFP) 6,800 ng/ml. Both HBs-Ag and HBs-Ab were negative. The patient died in a uremic state, with rapid increases of jaundice and ascites. Autopsy revealed gastric carcinoid with extensive metastases to the liver and the bone marrow. Tumor cells showed argyrophilia but not argentaffinity. Immunofluorescence specific for AFP was positive in the hepatocytes, particularly those adjacent to the metastatic tumor cells but not in the tumor cells, either primary or secondary. 79 cases reported in Japan of serum AFP-positive malignant tumor other than hepatocellular carcinoma and certain other malignancies of germ cell origin are reviewed and discussed.
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Kojima J, Kanatani M, Yamamoto T, Tateishi R, Nakamura N. Carcinoembryonic proteins in gastric carcinoma metastatic to the liver. GASTROENTEROLOGIA JAPONICA 1979; 14:596-603. [PMID: 93560 DOI: 10.1007/bf02773718] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Two cases of liver metastases from gastric carcinoma are described in which the simultaneous occurrences of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carcinoplacental alkaline phosphatase (CPALP) were demonstrated in the sera and tumor tissues. AFP was detected not only in the tumor tissues but also in the liver tissue adjacent to the tumor, while the other 2 carcinoembryonic proteins were not detected in the non cancerous liver tissues. The characteristics of CPALP in Case 1 were almost similar to the Nagao isoenzyme, based on enzyme tests involving L-leucine, L-phenylalanine and EDTA inhibitions, heat-stability and Michaelis constant, except for electrophoretical slower moving, while that in Case 2 were identical to variant type CPALP (Warnock).
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Abstract
Two hundred and eighty-four patients of various ages from an endemic area, diagnosed as having bilharziasis by the presence of living Schistosoma haematobium's ova in the mid-stream urine sample, have been investigated for the presence of alphafetoprotein (AFP) in the serum. One hundred and forty-one (49.6%), were positive; no false positives have occurred. Radioimmunoassay is capable of increasing the positivity rate still further. The detection of AFP will be of limited value as a screening test in countries where bilharziasis is endemic.
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Auer IO, Kress HG. Suppression of the primary cell-mediated immune response by human alpha1-fetoprotein in vitro. Cell Immunol 1977; 30:173-9. [PMID: 67903 DOI: 10.1016/0008-8749(77)90058-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Allen RP, Mizejewski GJ. Isolation and characterization of alpha-fetoprotein from the mouse hepatoma BW7756. BIOCHIMICA ET BIOPHYSICA ACTA 1977; 491:242-52. [PMID: 66068 DOI: 10.1016/0005-2795(77)90060-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Purification of alpha-fetoprotein from mouse hepatoma BW7756 extracts was performed using ammonium sulfate precipitations, gel filtration, ion-exchange chromatography and isoelectric focusing. These procedures produced a 5.6% yield of alpha-fetoprotein with 96% purity. Polyacrylamide slab gel electrophoresis, extended agarose electrophoresis and immunoelectrophoresis demonstrated that mouse hepatoma alpha-fetoprotein migrated at pH 8.6 as a rapid alpha1, or postalbumin globulin. Crossed antibody electrophoresis of the agarose zone containing alpha-fetoprotein failed to demonstrate microheterogeneity. Molecular weight analysis of the mouse hepatoma alpha-fetoprotein on a calibrated Sephadex G-200 column yielded a value of 72 000-73 000 for the native protein. Sodium dodecyl sulfate gel electrophoresis subsequently demonstrated a single polypeptide chain with a molecular weight of 72 000. Amino acid analysis showed the alpha-fetoprotein to be an acidic protein dominated by hydrophobic residues. The total carbohydrate content was 5.5%, and 3 mol of sialic acid were detected per mol of alpha-fetoprotein. Although neutral sugars were the principal class present, galactosamine was the most abundant single sugar detected.
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Okuda K, Kubo Y, Okazaki N, Arishima T, Hashimoto M. Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases. Cancer 1977; 39:232-46. [PMID: 64293 DOI: 10.1002/1097-0142(197701)39:1<232::aid-cncr2820390137>3.0.co;2-y] [Citation(s) in RCA: 181] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The clinical features of 57 autopsied cases of intrahepatic bile duct carcinoma including 28 cases of the peripheral type (cholangiocarcinoma in the narrow sense) and 29 cases of the hilar type are described in comparison with those of hepatocellular carcinoma, with a review of the literature on the clinicopathological aspects of intrahepatic bile duct carcinoma. As compared with hepatocellular carcinoma, the average age of the patients was older; the male predominance was not obvious, chronic parenchymal liver disease was infrequent in the past history, association of primary cirrhosis was seldom, cholestatic features were frequently the early signs and more pronounced during the course, the liver was enlarged to a lesser extent, ascites was less common, signs of portal hypertension were absent or minimal, and extrahepatic metastases were less frequent. In many respects, the hilar type resembled extrahepatic bile duct carcinoma, and the peripheral type was somewhat between it and hepatocellular carcinoma. Although the overall survival was not much different from that for hepatocellular carcinoma, early diagnosis is emphasized; this would make surgical management possible. Differential diagnosis from hepatocellular carcinoma may be possible in the majority with direct cholangiography, liver scan, celiac angiography, determination of alpha-fetoprotein and hepatitis B antigen, and blood chemistry such as SGOT, SLDH, serum bilirubin and alkaline phosphatase. Illustrative cases are given including one patient with a hilar carcinoma who survived for more than 2 years after transhepatic biliary drainage.
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REFERENCES. Scand J Immunol 1976. [DOI: 10.1111/j.1365-3083.1976.tb03848.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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CONCLUSION AND FUTURE RESEARCH. Scand J Immunol 1976. [DOI: 10.1111/j.1365-3083.1976.tb03167.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
Despite all the information about AFP presented, a great deal still needs to be discovered especially in pregnancy. Geographical and racial differences remain to be elucidated. Similarly, differences in obstetric population in Helsinki and Baltimore, for example, are only now being studied. Sex differences may exist; Lardinois and associates195 cited a higher level of AFP in male than female fetuses. The important questions that need to be answered are whether AFP assays can help improve the other half of prenatal care- that directed to the fetus- and whether the AFP model can help enhance our understanding of the similarities and differences of fetal and cancer cells.
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Goldenberg DM. Oncofetal and other tumor-associated antigens of the human digestive system. CURRENT TOPICS IN PATHOLOGY. ERGEBNISSE DER PATHOLOGIE 1976; 63:289-342. [PMID: 64333 DOI: 10.1007/978-3-642-66481-6_9] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Lamerz R, Fateh-Moghadam A. [Carcinofetal antigens. I. alpha-fetoprotein (author's transl)]. KLINISCHE WOCHENSCHRIFT 1975; 53:147-69. [PMID: 164580 DOI: 10.1007/bf01466760] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Alpha-fetoprotein (AFP) is an alpha1-glycoprotein (M.W. about 65000) appearing in the fetal serum of most mammals including man during the early stages of pregnancy; 4 weeks after birth it disappears altogether or exists at very low concentrations as in the normal adult. AFP is formed in the yolk sac, the fetal liver and the gastro-intestinal tract. One of its physiological functions in fetal life is supposed to be the protection of the fetus from maternal oestrogens (oestrophilic property). The clinical significance of AFP is based on the regular and increasing production in primary liver cell carcinoma, less frequently in teratogenetic tumors where it serves as a control of therapy and course of the disease. Less frequent, minor and temporary increases in the AFP serum level occur in several primary tumors with secondary liver involvement, and in inflammatory gastro-intestinal diseases, e.g. of the liver (hepatitis, cirrhosis). AFP has an increasing importance in gynecology (gestational age, fetal distress syndrom, malformations, hydatidiform mole/chorion carcinoma). The physico-chemical properties of AFP are widely known. Both fetal and tumor AFP appear to be immunologically and biochemically identical, as are that of tissue and biological fluids. The differences observed (variants, microheterogeneity) depend mainly on the different content of sialic acid. An antigenetic relationship exists, between the AFP of most species. The immunodiffusion (Ouchterlony) is the most frequently used but relatively insensitive test (1-5 mug/ml) in finding AFP, whereas the radioimmunoassay is the most sensitive one (up to 0,25 ng/ml) and permits the determination of normal serum levels in adults (below 20 ng/ml). The serum concentration in healthy pregnant women lies up to 500 ng/ml, in patients with hepatitis, liver cirrhosis and other liver diseases mostly under 3 mug/ml, whereas in those with primary liver cell carcinoma levels up to and above 600 mg-percent have been found.
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Seggie J, Gelfand M. Serum alpha-feto protein (alpha-FP) and hepatoma in Rhodesian Africans. Trans R Soc Trop Med Hyg 1975; 69:209-11. [PMID: 52210 DOI: 10.1016/0035-9203(75)90157-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Alpha-feto protein (alpha-FP) is now accepted as a very useful serum marker of hepatocarcinoma, and since its discovery in 1963, surveys have been carried out in various regions of the world, where hepatoma is particularly prevalent, which have shown that alpha-FP may be detected in 50 to 80% of patients with liver cancer. The sera of 30 Rhodesian African patients with histologically proven hepatoma were tested in this study for the presence of alpha-FP. In only 47% was alpha-FP detected. Thus it is our experience that a positive result is strong evidence in favour of a diagnosis of hepatocarcinoma whilst a negative result is of little value, necessitating that liver biopsy be carried out in all patients with clinical suspicion of liver cancer.
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Abstract
Two patients with primary gastric carcinoma and multiple liver secondaries who developed alpha fetoprotein in the serum are reported. Both had clinical features which were initially suggestive of primary liver cell carcinoma. Fetoprotein levels fell after ligation of the hepatic artery in one patient. Alpha fetoprotein may occur in the serum of adult patients with tumours of the foregut, other than primary liver cell carcinoma, when such tumours have metastasized to the liver.
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Vogel CL, Primack A, McIntire KR, Carbone PP, Anthony PP. Serum alpha-fetoprotein in 184 Ugandan patients with hepatocellular carcinoma. Clinical, laboratory, and histopathologic correlations. Cancer 1974; 33:959-64. [PMID: 4362109 DOI: 10.1002/1097-0142(197404)33:4<959::aid-cncr2820330410>3.0.co;2-v] [Citation(s) in RCA: 35] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Woodfield DG, Endo Y, Matsuhashi T. Primary liver cancer, alpha1 fetoprotein and hepatitis B antigen in Papua New Guinea. AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE 1974; 4:3-7. [PMID: 4135927 DOI: 10.1111/j.1445-5994.1974.tb03137.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Gitlin D, Perricelli A, Gitlin JD. The presence of serum alpha-fetoprotein in sharks and its synthesis by fetal gastrointestinal tract and liver. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. B, COMPARATIVE BIOCHEMISTRY 1973; 46:207-15. [PMID: 4127981 DOI: 10.1016/0305-0491(73)90311-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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