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Human Epidermal Receptor-2 Expression in Prostate Cancer¹

Department of Surgery, Divisions of Surgical Oncology [B. F. C.] and Urology [A. M. L., M. M., Q. F. C., C. W. G., J. L. M.], Department of Pathology and Laboratory Medicine [M. V. I., J. L. M.], Department of Pediatrics, Laboratories for Reproductive Biology [C. W. G.], Department of Medicine, Division of Hematology/Oncology [Y. E. W.], and the University of North Carolina–Lineberger Comprehensive Cancer Center [B. F. C., L. S. C., Y. L., Y. E. W., H. S. E., J. L. M.], University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Purpose: Efforts to conclusively establish that human epidermal receptor (HER)-2 overexpression is important to androgen-dependent carcinoma of the prostate (AD-CaP) or to progression to androgen independence (AI-CaP) have failed because of variability in tissue procurement, antibodies, immunostaining procedures, and assessment methods. However, because some in vitro and animal model data correlate HER-2 overexpression with progression to androgen independence, trials of agents that target the HER-2 receptor are under way. To clarify human tumor findings, we studied HER-2 expression at the gene (DNA), mRNA, and protein levels in well-characterized CaP specimens.

Experimental Design: Fifty AD-CaP and 25 AI-CaP specimens from similar numbers of Caucasian and African Americans were immunostained for HER-2 receptor. HER-2 mRNA levels were measured using real-time fluorescence quantitative PCR in patients for whom frozen specimens were available. HER-2 amplification was evaluated using fluorescent in situ hybridization.

Results: HER-2 receptor immunostained in 52% of androgen-dependent and one (4%) androgen-independent tumor. HER-2 immunostaining was not related to age, race, serum prostate-specific antigen levels, or pathologic stage and Gleason grade. HER-2 overexpression was not detected in AI-CaP at the mRNA or gene level. Mean HER-2 mRNA expression was higher (P < 0.05) in AD-CaP than AI-CaP (22,080 versus 15,496 HER-2 copies). HER-2 was not amplified in any of 20 AD-CaP or 19 AI-CaP specimens.

Conclusions: HER-2 protein and message overexpression and HER-2 amplification were not found in AI-CaP.

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