Type I receptor tyrosine kinases are associated with hormone escape in prostate cancer

被引:44
作者
Bartlett, JMS
Brawley, D
Grigor, K
Munro, AF
Dunne, B
Edwards, J
机构
[1] Glasgow Royal Infirm, Univ Dept Surg,Div Canc Sci & Mol Pathol, Sect Surg & Translat Res, Endocrine Canc Grp, Glasgow G31 2ER, Lanark, Scotland
[2] Western Gen Hosp, Dept Pathol, Edinburgh EH4 2XU, Midlothian, Scotland
[3] Glasgow Royal Infirm, Dept Pathol, Glasgow G31 2ER, Lanark, Scotland
关键词
prostate cancer; HER2 and EGFR; FISH; immunohistochemistry; hormone independence;
D O I
10.1002/path.1735
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Relapse during androgen withdrawal therapy is a significant cause of morbidity and mortality from prostate cancer. Androgen receptor mutations (6-10%) and amplifications (20-30%) may explain relapse in some patients, but in approximately 70% of cases, alternative mechanisms must be invoked and preliminary evidence suggests that type I receptor tyrosine kinases play a role in mediating hormone escape. In this study, EGFR and HER2 gene amplification and expression were analysed by fluorescence in situ hybridization and immunohistochemistry, respectively, in a cohort of matched tumour pairs (one taken before and one after hormone relapse) from 49 prostate cancer patients. No EGFR amplification and low-level, heterogeneous HER2 amplification were observed (6.5%). No significant correlation between EGFR/HER2 gene copy and protein expression was found. Almost one quarter of the cases (12/49, 24.5%) showed increased HER2 or EGFR expression at hormone relapse; this was associated with a significant reduction in time from hormone relapse to death (p = 0.0003). EGFR and HER2 amplification do not play a significant role in prostate cancer, but increased expression of HER2 or EGFR may influence progression to androgen independence in about a quarter of cases as a rise in EGFR/HER2 expression at hormone relapse is associated with a significant reduction in time to death. These findings support the development of EGFR/HER2 targeted therapies in androgen-independent prostate cancer and demonstrate, using a carefully characterized patient cohort, that the EGFR/HER2 pathway may represent one of a number of independent routes to hormone escape in prostate cancer. Copyright (C) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:522 / 529
页数:8
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