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

Authors

  • John MS Bartlett,

    Corresponding author
    1. Endocrine Cancer Research Group, Section of Surgical and Translational Research, Division of Cancer Sciences and Molecular Pathology, University Department of Surgery, Level II Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK
    • Endocrine Cancer Group, Section of Surgical and Translational Research, Division of Cancer Sciences and Molecular Pathology, University Department of Surgery, Level II Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK.
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  • Daniella Brawley,

    1. Endocrine Cancer Research Group, Section of Surgical and Translational Research, Division of Cancer Sciences and Molecular Pathology, University Department of Surgery, Level II Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK
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  • Ken Grigor,

    1. Department of Pathology, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK
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  • Alison F Munro,

    1. Endocrine Cancer Research Group, Section of Surgical and Translational Research, Division of Cancer Sciences and Molecular Pathology, University Department of Surgery, Level II Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK
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  • Barbara Dunne,

    1. Department of Pathology, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK
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  • Joanne Edwards

    1. Endocrine Cancer Research Group, Section of Surgical and Translational Research, Division of Cancer Sciences and Molecular Pathology, University Department of Surgery, Level II Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK
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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, 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.

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