Shh Overexpression Is Correlated with GRP78 and AR Expression in Primary Prostate Cancer: Clinicopathological Features and Outcomes in a Chinese Cohort.

Introduction: Shh plays an important role in prostate cancer progression, but its correlation with GRP78 and AR is elusive. Methods: The study included 539 patients in total, of which 443 had primary prostate carcinoma and 96 patients had benign prostatic hyperplasia (BPH). The clinicopathologic features, histologic scores of protein expression, and correlations between protein and disease state were studied in this cohort. Kaplan-Meier and Pearson correlation analyses were used to compare measures between groups. We performed immunohistochemistry to evaluate the expression of the Shh protein in benign prostatic hyperplasia (n=96) and prostate cancer (Gleason scores <= 6 [n=399] or >= 7 [n=44]). We quantified the expression of Shh, AR, and GRP78 using the weighted histoscore method, studied the correlation between Shh expression and AR and GRP78, and evaluated the impact of Shh protein expression on patient survival. Results: Shh expression was significantly higher in prostate cancer with Gleason scores >= 7 than in cancer with lower Gleason scores or benign hyperplasia and was much higher in AR-positive cancer than in AR-negative cancer. Shh is overexpressed in high-grade prostate cancer and is positively correlated with the expression of both GRP78 and AR. Conclusion: Therefore, Shh may be a useful prognostic marker and therapeutic target for prostate cancer.