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.
Cho
Kang Su
KS
Department of Urology & Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.
Lee
Joong Shik
JS
Cho
Nam Hoon
NH
Park
Kyeongmee
K
Ham
Won Sik
WS
Choi
Young Deuk
YD
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*
D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors