Seminal plasma proteins in prostatic carcinoma: increased nuclear semenogelin I expression is a predictor of biochemical recurrence after radical prostatectomy

Abstract

Semenogelins and eppin are seminal plasma proteins that form a complex and inhibit sperm motility. However, the role of these proteins in prostate cancer is poorly understood. We immunohistochemically stained for semenogelins I and II and eppin in 291 radical prostatectomy specimens. We then evaluated the association between their expressions in nuclei, cytoplasms, or intraluminal secretions of benign/high-grade prostatic intraepithelial neoplasia/carcinoma cells and clinicopathologic profile available for our patient cohort. Stains were positive in 32%/77%/84% (nuclear semenogelin I), 87%/94%/84% (nuclear semenogelin II), 56%/64%/37% (nuclear eppin), 7%/15%/11% (cytoplasmic semenogelin I), 6%/11%/9% (cytoplasmic semenogelin II), 68%/74%/95% (cytoplasmic eppin), 97%/98%/13% (secreted semenogelin I), 98%/97%/11% (secreted semenogelin II), and 97%/98%/48% (secreted eppin) of benign/prostatic intraepithelial neoplasia/carcinoma, respectively. The levels of nuclear semenogelin I/cytoplasmic eppin were significantly higher in carcinoma than in benign (P<.001/P<.001) or prostatic intraepithelial neoplasia (P<.001/P<.001) and in prostatic intraepithelial neoplasia than in benign (P<.001/P=.006). Significantly higher nuclear semenogelin II expression was found in prostatic intraepithelial neoplasia than in benign (P<.001) or carcinoma (P<.001). Significantly lower nuclear eppin expression was seen in carcinoma than in benign (P<.001) or prostatic intraepithelial neoplasia (P<.001). Secreted semenogelin I, secreted semenogelin II, and secreted eppin were all significantly lower in carcinoma than in benign (P<.001) or prostatic intraepithelial neoplasia (P<.001). There were no statistically significant correlations between each stain and clinicopathologic features except significantly lower nuclear eppin expression in Gleason score 8 or higher tumors. Kaplan-Meier and log-rank tests further revealed that patients with nuclear semenogelin I-positive tumor had a significantly higher risk for biochemical recurrence (P=.046). Multivariate Cox model showed a trend toward significance (P=.093) in nuclear semenogelin I positivity as an independent predictor for recurrence. These results suggest that nuclear semenogelin I expression could be a reliable prognosticator in men who undergo radical prostatectomy.