C-MYC AMPLIFICATION IN HEPATOCELLULAR CARCINOMA PREDICTS UNFAVORABLE PROGNOSIS

Abstract Structural alterations and amplifications of the c-myc oncogene have been implicated in the pathogenesis and progression of several human neoplastic diseases. To study the role of c-myc amplification in human hepatocellular carcinomas (HCC), we analyzed 20 HCC using differential polymerase chain reaction (PCR). DNA used for differential PCR was extracted from formalin-fixed, paraffin-embedded tissue obtained by radiographically directed needle aspiration biopsy. Differential PCR reactions included sets of primers for c-myc and a control gene, dopamine D2 receptor (D2R), which yielded products of 150 bp and 110 bp, respectively. Evaluation of amplification was based on the relative concentration of c-myc and D2R PCR products. The c-myc amplification was detected in 10 of 20 HCC. Cases with c-myc amplification tended to have higher histologic grade and were significantly (P = 0.05) associated with worse prognosis. Amplification was present in none of two Grade 1 tumors, seven of the fourteen Grade 2 tumors, and three of four Grade 3 tumors. The mean survival times (+/- SEM) for patients with and without c-myc amplification were 5.7 (+/- 1.8) and 13.8 (+/- 2.6) months, respectively. These results indicate that c-myc amplification in HCC can be evaluated by differential PCR of needle biopsy specimens, and is an unfavorable prognostic indicator.