The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer

Edwards, J., Traynor, P., Munro, A., Pirrett, C.F., Dunne, B. and Bartlett, J.M.S. (2006) The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer. Clinical Cancer Research, 12(1), pp. 123-130. (doi: 10.1158/1078-0432.CCR-05-1445)

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Publisher's URL: http://dx.doi.org/10.1158/1078-0432.CCR-05-1445

Abstract

<b>Purpose</b>: The role of the type I receptor tyrosine kinase (HER) family in progression of prostate cancer is controversial. Breast cancer studies show that these receptors should be investigated as a family. The current study investigates expression of HER1-HER4 and EGFRvIII in matched hormone-sensitive and hormone-refractory prostate tumors. <b>Experimental Design</b>: Immunohistochemical analysis was used to investigate protein expression of HER1-HER4, EGFRvIII, and phosphorylated Akt (pAkt) in matched hormone-sensitive and hormone-refractory prostate tumors. <b>Results</b>: Surprisingly, high HER2 membrane expression in hormone-sensitive tumors was associated with an increased time to biochemical relapse (<i>P</i> = 0.0003), and this translated into longer overall survival (<i>P</i> = 0.0021). Consistent with other studies, HER4 membrane expression in hormone-sensitive tumors was associated with longer time to biochemical relapse (<i>P</i> = 0.042), and EGFRvIII membrane expression was associated with shorter time to biochemical relapse (<i>P</i> = 0.015). An increase in pAkt expression was associated with reduced survival (<i>P</i> = 0.0098). Multivariate analysis showed that HER2 was an independent positive predictive marker of time to relapse in hormone-sensitive prostate tumors (<i>P</i> = 0.014). In contrast, high HER2 expression in hormone-refractory tumors was associated with decreased time to death from biochemical relapse (<i>P</i> = 0.039), and EGFRvIII nuclear expression was associated with decreased time to death from biochemical relapse and decreased overall survival (<i>P</i> = 0.02 and <i>P</i> = 0.005). <b>Conclusion</b>: These results suggest that the HER family may have multiple roles in prostate cancer, and that expression of the proteins alone is insufficient to predict the biological response that they may elicit.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Edwards, Professor Joanne and McCall, Dr Pamela and Munro, Ms Alison
Authors: Edwards, J., Traynor, P., Munro, A., Pirrett, C.F., Dunne, B., and Bartlett, J.M.S.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Clinical Cancer Research
Publisher:American Association for Cancer Research
ISSN:1078-0432
ISSN (Online):1557-3265
Copyright Holders:Copyright © 2006 American Association for Cancer Research
First Published:First published in Clinical Cancer Research 12(1):123-130
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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