Amplification of c-myc in hepatocellular carcinoma: Correlation with clinicopathologic features, proliferative activity and p53 overexpression

Expression of the proto-oncogene c-myc has been implicated in liver regener ation and hepatocarcinogenesis. The biologic significance of c-myc gene amp lification in human hepatocellular carcinoma, however, is unconfirmed. We c orrelated c-myc gene amplification with clinicopathologic features, prolife rative activity, and p53 expression in 42 resected tumors. c-myc amplificat ion in tumor tissue was determined using a differential polymerase chain re action, a useful procedure for the evaluation of gene amplification in arch ival formalin-fixed paraffin-embedded tissues, in comparison with a dopamin e D2 receptor gene. Proliferative activity was estimated by numbers of argy rophilic nucleolar organizer regions and immunohistochemical nuclear labeli ng rates using a monoclonal antibody against Ki-67. The c-myc gene was ampl ified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. N o correlation was noted with a-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activ ity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplificatio n. These results suggest that c-myc amplification is an indicator of malign ant potential and poor prognosis in hepatocellular carcinoma. c-myc amplifi cation and p53 alteration may be coparticipating events in the progression of these tumors.