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Type I receptor tyrosine kinases are associated with hormone escape in prostate cancer
Author(s) -
Bartlett John MS,
Brawley Daniella,
Grigor Ken,
Munro Alison F,
Dunne Barbara,
Edwards Joanne
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1735
Subject(s) - prostate cancer , androgen receptor , medicine , oncology , cancer , cancer research , prostate , androgen , immunohistochemistry , hormone , endocrinology
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 © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.