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

J Pathol. 2005 Mar;205(4):522-9. doi: 10.1002/path.1735.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / physiology
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Gene Amplification
  • Genes, erbB / genetics*
  • Genes, erbB-1 / genetics
  • Genes, erbB-2 / genetics
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization, Fluorescence / methods
  • Male
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / physiopathology
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Retrospective Studies
  • Survival Analysis


  • Androgens
  • Receptor Protein-Tyrosine Kinases