Gene amplification and mutation analysis of epidermal growth factor receptor in hormone refractory prostate cancer

BACKGROUND. Amplification and mutation of the epidermal growth factor receptor (EGFR) and Her-2 genes were analyzed in both hormone sensitive and hormone refractory prostate cancer (HRPC). METHODS. Gene amplifications of EGFR and Her-2 were analyzed by fluorescence in situ hybridization (FISH) with direct sequencing. Studies were performed on a total of 10 patients; tissues were sampled at the time of initial diagnosis and after the conversion to HRPC (a total of 20 tissue samples). Direct sequencing was performed on exons 18-24 of EGFR and exons 19 and 20 of Her-2. Amplification and mutation were compared with clinicopathologic features. RESULTS. Gene amplification of EGFR was observed in 6 (30%) out of 20 samples. A total of six EGFR mutations in exons 18 and 19 were detected in three pairs of tissues (three patients). One patient, with hormone refractory status, had a novel deletion mutation in EGFR exon 19. EGFR mutations were associated with the acinar type of prostate cancer but were not associated with the ductal type. No significant correlation was found between mutation change and hormone sensitive or refractory status. However, the time to convert to HRPC was significantly shorter in the patients with a mutation in the EGFR gene (P = 0.017). There were no Her-2 gene amplifications or mutations found in any of the samples. CONCLUSIONS. EGFR gene mutation and amplification occurred frequently in advanced prostate cancer cases. EGFR mutations do not appear to play a significant role in the hormone refractory pathway but are associated with prognosis.