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Journal of Histochemistry and Cytochemistry, Vol. 45, 79-88, Copyright © 1997 by The Histochemical Society, Inc.

ARTICLE

Expression of HGF, Its Receptor c-met, c-myc, and Albumin in Cirrhotic and Neoplastic Human Liver Tissue

Julia Y. Ljubimovaa, Lidija M. Petrovicb, Steven E. Wilsonc, Stephen A. Gellerb, and Achilles A. Demetrioua
a Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
b Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
c Department of Ophthalmology, Cleveland Clinic Foundation, Cleveland, Ohio

Correspondence to: Julia Y. Ljubimova, Surgical Research, Cedars-Sinai Medical Center, D-4018, 8700 Beverly Blvd., Los Angeles, CA 90048.

Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver. (J Histochem Cytochem 45:79-87, 1997)

Key Words: Hepatocyte growth factor, c-met, c-myc, Albumin, Gene expression, PCR, Immunofluorescence, Cirrhosis, Hepatocellular carcinoma


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