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

Bartlett, J.M., Brawley, D., Grigor, K.M., Munro, A.F., Dunne, B. and Edwards, J. (2005) Type I receptor tyrosine kinases are associated with hormone escape in prostate cancer. Journal of Pathology, 205(4), pp. 522-529. (doi: 10.1002/path.1735)

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Publisher's URL: http://dx.doi.org/10.1002/path.1735

Abstract

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, <i>EGFR</i> and <i>HER2</i> gene amplification and expression were analysed by fluorescence <i>in situ</i> 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 <i>EGFR</i> amplification and low-level, heterogeneous <i>HER2</i> amplification were observed (6.5%). No significant correlation between <i>EGFR/HER2</i> 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 (<i>p</i> = 0.0003). <i>EGFR</i> and <i>HER2</i> 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Edwards, Professor Joanne
Authors: Bartlett, J.M., Brawley, D., Grigor, K.M., Munro, A.F., Dunne, B., and Edwards, J.
Subjects:R Medicine > RB Pathology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Pathology
Journal Abbr.:J. pathol.
ISSN:0022-3417
ISSN (Online):1096-9896
Published Online:31 January 2005

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