Clinical Significance of Wnt/beta-Catenin Signalling and Androgen Receptor Expression in Prostate Cancer

ABSTRACT

PURPOSE: To investigate the relationships among the Wnt/beta-catenin pathway, androgen receptor (AR), and clinicopathological factors in hormone-naive prostate cancer. MATERIALS AND METHODS: This study was conducted with132 cases of hormone-naive prostate cancer treated by prostatectomy and prostate needle biopsy. An immunohistochemical study using antibodies against beta-catenin, matrix metalloproteinase-7 (MMP-7), and the AR was performed. For the in vitro study, PC-3, LNCaP, 22Rv1, and DU145 cell lines were used. RESULTS: The clinical or pathological stage ware a localized cancer in 36 patients (27.3%), locally advanced cancer in 31 (23.5%), and metastatic cancer in 65 (49.2%). We detected increased beta-catenin, AR, and MMP-7 expression with a high Gleason grade, disease progression, and increasing serum prostate-specific antigen (PSA) levels (p<0.01). In Spearman's rank correlations, the expression of cytoplasmic beta-catenin, MMP-7, and the AR were found to be significantly positively correlated. In addition, the expression of beta-catenin, MMP-7, and the AR were significantly correlated with clinicopathological variables indicative of a poor prognosis. Forty-nine patients with primary androgen deprivation had short response durations from hormone therapy to PSA progression with elevated MMP-7 expression on the Kaplan-Meier curve (p=0.0036). CONCLUSIONS: These data show that an activated Wnt/beta-catenin pathway and AR expression in prostate cancer are correlated with metastasis and aggressiveness. In addition, the expression of MMP-7 protein, a target of the Wnt/beta-catenin pathway, is associated with PSA progression in prostate cancer patients undergoing primary hormone therapy.