Seminal Plasma Proteins in Prostate Cancer: Increased Semenogelin I Expression Is a Predictor of Biochemical Recurrence after Radical Prostatectomy
Koji Izumi, Yi Li, Yichun Zheng, Qi Yang, Loralee A McMahon, Jennifer Gordetsky, Jorge L Yao, Hiroshi Miyamoto. University of Rochester, Rochester, NY
Background: Semenogelins, predominantly expressed and secreted by the seminal vesicle, are the main structural proteins in human semen coagulum. Eppin (epidermal protease inhibitor), specifically expressed and secreted by the epididymis and testis, has been known to bind to semenogelin, resulting in inhibition of sperm motility. However, the role of these seminal plasma proteins in prostate cancer is poorly understood.
Design: We immunohistochemically stained for semenogelins I (SgI) and II (SgII) and eppin in 291 radical prostatectomy specimens. We then evaluated the association between their expressions in nuclei (n-), cytoplasms (c-), or intraluminal secretions (s-) of benign (BN)/high-grade prostatic intraepithelial neoplasia (PIN)/carcinoma (CA) cells and clinicopathologic profiles available for our patient cohort.
Results: Stains were positive in 32%/77%/84% (n-SgI), 87%/94%/84% (n-SgII), 56%/64%/37% (n-eppin), 7%/15%/11% (c-SgI), 6%/11%/9% (c-SgII), 68%/74%/95% (c-eppin), 97%/98%/13% (s-SgI), 98%/97%/11% (s-SgII), and 97%/98%/48% (s-eppin) of BN/PIN/CA, respectively. The levels of n-SgI and c-eppin were significantly higher in CA than in BN (P<0.001 and P<0.001) or PIN (P=0.065 and P=0.001) and in PIN than in BN (P<0.001 and P=0.145). Significantly higher n-SgII expression was found in PIN than in BN (P=0.028) or CA (P=0.002). Significantly lower n-eppin expression was seen in CA than in BN (P<0.001) or PIN (P<0.001). s-SgI, s-SgII, and s-eppin were all significantly lower in CA than in BN (P<0.001) or PIN (P<0.001). There were no statistically significant correlations between each stain and clinicopathologic features, such as Gleason score, pathologic stage (pT/pN), and preoperative prostate-specific antigen (PSA) levels, except higher PSA in patients with n-SgI(+) tumor than in those with n-SgI(-) tumor (P=0.017). Kaplan-Meier and log-rank tests further revealed that patients with n-SgI(+) tumor had a higher risk for biochemical (PSA) recurrence (P=0.046). Multivariate Cox model showed a trend toward significance (P=0.091) in n-SgI positivity as an independent predictor for recurrence.
Conclusions: Compared to non-neoplastic prostate and PIN tissues, significantly increased (n-SgI and c-eppin) or decreased (n-eppin) expression was seen in prostate cancer. Our results suggest the involvement of semenogelins and eppin in prostate cancer development and progression. Moreover, SgI expression could be a reliable prognosticator in men who undergo radical prostatectomy.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 109, Tuesday Afternoon