Purpose: Amplification and mutation of the epidermal growth factor receptor (EGFR) and HER-2 genes were analyzed in the tissues of hormone refractory prostate cancer (HRPC) patients. Materials and Methods: Gene amplifications of the EGFR and HER-2 gene were analyzed by fluorescence in situ hybridization (FISH) with direct sequencing. Studies were performed on 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 the EGFR gene and exons 19 and 20 of the HER-2 gene. The amplifications and mutations were compared with the clinicopathologic features. Results: Gene amplification of the EGFR gene 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 a hormone refractory status had a novel deletion mutation in EGFR exon 19. EGFR mutations were associated with the acinar type of prostate cancer, but they were not associated with the ductal type. No significant correlation was found between mutation change and the 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 these advanced prostate cancer cases, but EGFR mutations do not appear to play a significant role in the hormone refractory pathway. However, EGFR gene mutation is closely associated with the time to convert to HRPC.
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