Endothelin-1 expression in prostate cancer and high grade prostatic intraepithelial neoplasia.

Objective: To investigate the prognostic value of endothelin-1 (ET-1), a vasoconstrictor involved in differentiation and growth of cancer, in prostate cancer.

Study Design: A tissue microarray was constructed of 287 prostate cancers from radical prostatectomy (RP) specimens with median follow-up of 48.9 months. Slides were immunostained for ET-1. Intensity and extent of immunoreactivity and their product (IRp) were evaluated. We separately arrayed benign prostatic tissue, atrophy, high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer from 40 men.

Results: ET-1 expression was stronger in both HGPIN and cancer than in benign tissue (p < 0.001). The intensity and the IRp of ET-1 predicted biochemical recurrence (p < 0.001 and p = 0.044, respectively), while the staining extent showed no significant correlation with outcome (p = 0.68). Recurrence-free survival in patients with strong ET-1 staining was shorter than in those with weaker expression (hazard ratio [CI 95%] 2.44 [1.55-3.84], p < 0.001). In a multivariate analysis including ET-1 expression, preoperative serum prostate-specific antigen (PSA), extraprostatic extension, margin status, seminal vesicle invasion and Gleason score, only PSA, margins and Gleason score remained significant.

Conclusion: ET-1 is overexpressed in localized prostate cancer and predicts outcome after RP in univariate analysis.