Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray

BACKGROUND: Amplifications of 1q21, c-myc at 8q24.1, and AIB1 at 20q12 are genetic alterations that are detected frequently in hepatocellular carcinoma (HCC). The authors evaluated the association of these amplifications with the prognosis of patients with HCC. METHODS: In the current study, amplification of 1q21, c-myc, and AIB1 was analyzed in 560 specimens from 400 patients with HCC and 20 patients with benign liver lesions using fluorescence in situ hybridization with high-throughput tissue microarray. Differences of amplification patterns were compared between small and large HCC, single nodular and multiple nodular HCC, primary and metastatic HCC, and primary and recurrent HCC. RESULTS: Significant differences between single nodular and multiple nodular HCC were detected in c-myc amplification (12% vs. 38%; P < 0.01) and AIB1 amplification (16% vs. 30%; P < 0.05). More frequent c-myc amplification was detected in metastatic HCC (45%) compared with primary HCC (29%) and in recurrent HCC (60%) compared with primary HCC (38%). Similarly, more frequent AIB1 amplification was observed in metastatic HCC (41%) compared with primary HCC (23%) and in recurrent HCC (60%) compared with primary HCC (29%). However, no significant differences in 1q21 amplification were observed. CONCLUSIONS: The current results strongly suggest that amplifications of the c-myc and AIB1 oncogenes are late genetic alterations in the progression of HCC and are correlated with a poor prognosis.