The influence of testosterone suppression on HER2 immunoexpression in prostatic neoplastic tissue

During initial risk assessments, the metastatic potential of prostate cancer (PCa) may not be fully considered. The tumor's multicentric origin, which is associated with genetic mutations, may explain existing treatment limitations. Investigating human epidermal growth factor receptor 2 (HER2) expression in patients with different stages of PCa may therefore increase understanding of the mechanisms associated with the development of castration resistance. The present study examined the association between HER2 expression and the histologic features of PCa subjected to radical prostatectomy (RP) and evaluated the role of testosterone suppression in HER2 expression. In group 1, specimens from individuals who underwent RP without prior neoadjuvant androgen deprivation therapy (ADT) were included (n=42). In group 2 (PCa with ADT), specimens from individuals who underwent RP and received neoadjuvant cyproterone acetate during distinct periods (200 mg daily for 1-24 months) were included (n=150; cohort derived from a previous study). Immunohistochemical expression of HER2 was associated with prognostic factors such as perineural invasion, extra-prostatic disease, T stage, serum prostate-specific antigen (PSA), angiolymphatic invasion and surgical margins. Univariate regression analysis indicated that perineural invasion, PSA, International Society of Urological Pathology, angiolymphatic invasion, margin, T stage and neoadjuvant ADT was associated with HER2 expression. Ordinal regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (P<0.001). In addition, regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (odd ratio=0.01; 95% CI, 0.00, 0.02; P<0.001). HER2 was expressed in PCa samples but was not associated with known prognostic factors. The use of short-acting ADT and the consequent blockage of testosterone effect may suppress the expression of HER2 in PCa cells.