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Annals of Oncology Advance Access published online on November 12, 2007
Annals of Oncology, doi:10.1093/annonc/mdm490
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© 2007 European Society for Medical Oncology

Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel

J. Domingo-Domenech1, P. L. Fernandez2, X. Filella3, A. Martinez-Fernandez1, R. Molina3, E. Fernandez2, A. Alcaraz4, J. Codony1, P. Gascon1 and B. Mellado1,*

1 Department of Medical Oncology and Laboratory of Experimental Oncology, Institut Clínic de Malalties Hemato-Oncològiques
2 Department of Pathology
3 Department of Biochemistry, Centre Diagnostic Biomèdic
4 Department of Urology, Institut d' Investigacions Biomèdiques Agust Pi i Sunyer, University of Barcelona, Hospital Clinic, Barcelona, Spain

* Correspondence to: Dr B. Mellado, Hospital Clinic i Provincial—Medical Oncology Villarroel, 130 Barcelona 08901, Spain. Tel: +34-932275400 Fax: +34-934546520; E-mail: bmellado{at}clinic.ub.es

Background: Human epidermal growth factor receptor 2 (HER2) overexpression has been linked to hormone-independent prostate cancer (HIPC) progression. Its clinical value and correlation with therapy is not defined.

Patients and methods: Patients with HIPC treated with docetaxel (Taxotere) were prospectively tested for serum HER2 extracellular domain (ECD) by immunoanalysis. HER2 was determined by immunohistochemistry and FISH in tumor samples.

Results: Sixty-nine patients were included. Twenty-four (34.8%) patients had high HER2 ECD (>15 ng/ml). Prostate-specific antigen (PSA) response was 58% for patients with low HER2 ECD and 36% for patients with high HER2 ECD (P = 0.046). HER2 ECD levels were an independent prognostic factor for time to PSA progression [hazard ratio (HR) 2.82; confidence interval (CI) 95% 1.22–6.50; P = 0.015] and overall survival (HR 3.24; CI 95% 1.38–7.59; P = 0.007). Tissue samples from 17 patients were tested for HER2. Patients with negative HER2 tissue expression had lower HER2 ECD levels (median 10.5 ± 2.7 versus 30.5 ± 24.8 ng/ml; P = 0.016). FISH was negative in all samples.

Conclusions: High HER2 ECD levels in serum are associated with a worst clinical outcome of HIPC patients treated with docetaxel.

docetaxel, HER2, HER2 ECD, hormone-independent prostate cancer

Received for publication June 27, 2007. Revision received August 18, 2007. Accepted for publication September 18, 2007.


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