RELATIONSHIP BETWEEN LOSS OF HETEROZYGOSITY OF TUMOR-SUPPRESSOR GENESAND HISTOLOGIC DIFFERENTIATION IN HEPATOCELLULAR-CARCINOMA

BACKGROUND. Hepatocellular carcinoma (HCC) is one of the most common h uman tumors in Asia and Africa. The molecular genetic changes involvin g both protooncogenes and tumor suppressor genes are known to be invol ved in hepatocarcinogenesis, but the roles of the known tumor suppress or genes in hepatocarcinogenesis GROUND, Hepatocellular carcinoma (HCC ) is one of the most common human are not fully elucidated. In this st udy, the authors analyzed the loss of heterozygosity (LOH) of known tu mor suppressor genes in HCC and evaluated the relationship between LOH of tumor suppressor genes and clinicopathologic features. METHODS. Th e authors assessed the LOH of the 10 known tumor suppressor genes (VHL , APC, EXT1, WT1, Rbl, p53, BRCA1, nm23, DPC4, and DCC) with microsate llite markers in 29 consecutively resected HCC specimens. RESULTS. The authors found frequent LOH of tumor suppressor genes in HCC. Twenty f ive of 29 cases (86%) had LOH of tumor suppressor genes and 17 cases ( 59%) had LOHs involving 2-4 tumor suppressor genes. Among the tumor su ppressor genes, frequent LOH was noted in the p53 (66%), Rbl (33%), EX T1 (33%), and APC (20%) genes. LOH of the p53 gene and multiple LOH of the tumor suppressor genes were more frequent in poorly differentiate d HCCs (P = 0.02). CONCLUSIONS. The LOH of tumor suppressor genes is f requent in HCCs and LOH of the p53 gene and accumulated LOHs are relat ed to poorly differentiated HCC. Abnormalities of the p53 gene or the accumulated abnormalities of the tumor suppressor genes may play a rol e in the aggressive progression of HCC. (C) 1997 American Cancer Socie ty.