Abstract
OBJECTIVE: The objective of this study was to analyze the specificity of detecting liver tumor cell dissemination by alpha-fetoprotein (AFP) mRNA in peripheral blood. SUMMARY BACKGROUND DATA: Alpha-fetoprotein mRNA has been used for the detection of circulating micrometastatic tumor foci of hepatocellular carcinoma (HCC); however, the interpretation of the results has been equivocal. METHODS: Sixty-four consecutive patients with malignant HCC (n = 20), liver metastases (n = 27), or nonmalignant (n = 17) liver diseases undergoing partial or total hepatectomy and orthotopic liver transplantation were included in this prospective study from January to July 1995. Peripheral blood samples were obtained before surgery, during surgery, and after surgery (range, 6-15 months). Total mRNA was extracted from nucleated cells, and cDNA synthesis and polymerase chain reaction amplification (nested polymerase chain reaction in one tube) were performed with specific AFP primers. RESULTS: Preoperative AFP mRNA was detected in 20 patients (17%), of which 5 of 20 had HCC. Intraoperative assessment showed positive AFP mRNA values in a total of 34 patients (53%) with various causes, of which 8 of 20 (40%) had HCC, 17 of 27 (63%) had other malignancies, and 9 of 17 (53%) had nonmalignant diseases. Recurrent tumor in patients with HCC occurred in four cases after surgery (range, 6-15 months) and did not correlate with AFP mRNA positivity before surgery, during surgery, or after surgery. CONCLUSIONS: Alpha-fetoprotein mRNA in peripheral blood is not a specific marker of circulating micrometastases from HCC, especially in the context of surgical treatment of HCC.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brown D. C., Purushotham A. D., Birnie G. D., George W. D. Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction. Surgery. 1995 Jan;117(1):95–101. doi: 10.1016/s0039-6060(05)80235-1. [DOI] [PubMed] [Google Scholar]
- Carr B. I. An assay for micrometastatic hepatocellular carcinoma. Gastroenterology. 1994 Jan;106(1):264–267. doi: 10.1016/s0016-5085(94)96201-4. [DOI] [PubMed] [Google Scholar]
- Chelly J., Concordet J. P., Kaplan J. C., Kahn A. Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2617–2621. doi: 10.1073/pnas.86.8.2617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chou H. C., Sheu J. C., Huang G. T., Wang J. T., Chen D. S. Albumin messenger RNA is not specific for circulating hepatoma cells. Gastroenterology. 1994 Aug;107(2):630–631. doi: 10.1016/0016-5085(94)90205-4. [DOI] [PubMed] [Google Scholar]
- Farmer D. G., Rosove M. H., Shaked A., Busuttil R. W. Current treatment modalities for hepatocellular carcinoma. Ann Surg. 1994 Mar;219(3):236–247. doi: 10.1097/00000658-199403000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fidler I. J. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo-2'-deoxyuridine. J Natl Cancer Inst. 1970 Oct;45(4):773–782. [PubMed] [Google Scholar]
- Frenoy N., Chabli A., Sol O., Goldschmit E., Lemonnier M. P., Misset J. L., Debuire B. Application of a new protocol for nested PCR to the detection of minimal residual bcr/abl transcripts. Leukemia. 1994 Aug;8(8):1411–1414. [PubMed] [Google Scholar]
- Gibbs P. E., Zielinski R., Boyd C., Dugaiczyk A. Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene. Biochemistry. 1987 Mar 10;26(5):1332–1343. doi: 10.1021/bi00379a020. [DOI] [PubMed] [Google Scholar]
- Glaves D., Huben R. P., Weiss L. Haematogenous dissemination of cells from human renal adenocarcinomas. Br J Cancer. 1988 Jan;57(1):32–35. doi: 10.1038/bjc.1988.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hillaire S., Barbu V., Boucher E., Moukhtar M., Poupon R. Albumin messenger RNA as a marker of circulating hepatocytes in hepatocellular carcinoma. Gastroenterology. 1994 Jan;106(1):239–242. doi: 10.1016/s0016-5085(94)95705-3. [DOI] [PubMed] [Google Scholar]
- Israeli R. S., Miller W. H., Jr, Su S. L., Powell C. T., Fair W. R., Samadi D. S., Huryk R. F., DeBlasio A., Edwards E. T., Wise G. J. Sensitive nested reverse transcription polymerase chain reaction detection of circulating prostatic tumor cells: comparison of prostate-specific membrane antigen and prostate-specific antigen-based assays. Cancer Res. 1994 Dec 15;54(24):6306–6310. [PubMed] [Google Scholar]
- Kar S., Carr B. I. Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma. Hepatology. 1995 Feb;21(2):403–407. [PubMed] [Google Scholar]
- Komeda T., Fukuda Y., Sando T., Kita R., Furukawa M., Nishida N., Amenomori M., Nakao K. Sensitive detection of circulating hepatocellular carcinoma cells in peripheral venous blood. Cancer. 1995 May 1;75(9):2214–2219. doi: 10.1002/1097-0142(19950501)75:9<2214::aid-cncr2820750905>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- Leather A. J., Gallegos N. C., Kocjan G., Savage F., Smales C. S., Hu W., Boulos P. B., Northover J. M., Phillips R. K. Detection and enumeration of circulating tumour cells in colorectal cancer. Br J Surg. 1993 Jun;80(6):777–780. doi: 10.1002/bjs.1800800643. [DOI] [PubMed] [Google Scholar]
- Leather A. J., Gallegos N. C., Kocjan G., Savage F., Smales C. S., Hu W., Boulos P. B., Northover J. M., Phillips R. K. Detection and enumeration of circulating tumour cells in colorectal cancer. Br J Surg. 1993 Jun;80(6):777–780. doi: 10.1002/bjs.1800800643. [DOI] [PubMed] [Google Scholar]
- Lévi F. A., Zidani R., Vannetzel J. M., Perpoint B., Focan C., Faggiuolo R., Chollet P., Garufi C., Itzhaki M., Dogliotti L. Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial. J Natl Cancer Inst. 1994 Nov 2;86(21):1608–1617. doi: 10.1093/jnci/86.21.1608. [DOI] [PubMed] [Google Scholar]
- Macfarlane D. E., Dahle C. E. Isolating RNA from whole blood--the dawn of RNA-based diagnosis? Nature. 1993 Mar 11;362(6416):186–188. doi: 10.1038/362186a0. [DOI] [PubMed] [Google Scholar]
- Matsumura M., Niwa Y., Hikiba Y., Okano K., Kato N., Shiina S., Shiratori Y., Omata M. Sensitive assay for detection of hepatocellular carcinoma associated gene transcription (alpha-fetoprotein mRNA) in blood. Biochem Biophys Res Commun. 1995 Feb 15;207(2):813–818. doi: 10.1006/bbrc.1995.1259. [DOI] [PubMed] [Google Scholar]
- Matsumura M., Niwa Y., Kato N., Komatsu Y., Shiina S., Kawabe T., Kawase T., Toyoshima H., Ihori M., Shiratori Y. Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma. Hepatology. 1994 Dec;20(6):1418–1425. doi: 10.1002/hep.1840200607. [DOI] [PubMed] [Google Scholar]
- Mayhew E., Glaves D. Quantitation of tumorigenic disseminating and arrested cancer cells. Br J Cancer. 1984 Aug;50(2):159–166. doi: 10.1038/bjc.1984.158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moreno J. G., Croce C. M., Fischer R., Monne M., Vihko P., Mulholland S. G., Gomella L. G. Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res. 1992 Nov 1;52(21):6110–6112. [PubMed] [Google Scholar]
- Naito H., Kuzumaki N., Uchino J., Kobayashi R., Shikano T., Ishikawa Y., Matsumoto S. Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by the reverse transcription-polymerase chain reaction. Eur J Cancer. 1991;27(6):762–765. doi: 10.1016/0277-5379(91)90184-f. [DOI] [PubMed] [Google Scholar]
- Okuda K. Hepatocellular carcinoma: recent progress. Hepatology. 1992 May;15(5):948–963. doi: 10.1002/hep.1840150532. [DOI] [PubMed] [Google Scholar]
- Pichard L., Fabre I., Daujat M., Domergue J., Joyeux H., Maurel P. Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Mol Pharmacol. 1992 Jun;41(6):1047–1055. [PubMed] [Google Scholar]
- Smith B., Selby P., Southgate J., Pittman K., Bradley C., Blair G. E. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet. 1991 Nov 16;338(8777):1227–1229. doi: 10.1016/0140-6736(91)92100-g. [DOI] [PubMed] [Google Scholar]