2336 EXPRESSION OF SEMINAL PLASMA PROTEINS IN PROSTATE CANCER: PROGNOSTIC IMPLICATIONS AFTER RADICAL PROSTATECTOMY

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reported genomic amplification and overexpression of PSAP in androgen-independent and metastatic prostate cancer (PCa) cells, xenografts, and metastatic lymph nodes. Here, we examined the association between tissue expression/serum-PSAP levels and PCa progression. METHODS: We established a highly sensitive sandwich-ELISA assay to measure serum-PSAP. We determined serum-PSAP levels in an age-adjusted normal male population (n⫽90) and in a cohort of 110 patients with primary or metastatic and/or hormone-refractory PCa. In addition, by using immunohistochemical (IHC) staining and tissue microarrays comprised of 154 PCa cases with 96 parallel BPH samples, we examined the intensity of anti-PSAP staining and its association with clinicohistopathological variables. RESULTS: In univariate analysis, using Cochran-Mantel-Haenszel statistics (ANOVA row mean scores), we found that the average PSAP staining score in malignant tumors differs significantly based on clinical stage II and III (p ⫽ 0.0415), dominant Gleason pattern 3 and 4 (p ⫽ 0.0119), and seminal vesicle invasion status (p ⫽ 0.0091). In multivariate analysis, after adjusting for serum-PSAP levels, we detected an association between PSAP expression and dominant Gleason patterns 3 and 4 (p ⫽ 0.0144). This association was statistically significant (p ⫽ 0.0264) for serum-PSAP ⬍ 4.0 ng/ml only. In the normal male population (n⫽89), the lowest serum-PSAP level was detected at age ⬍13 y/o; yet it peaked for ages 20-39 y/o and then, decreased to the levels between these two age groups for men above 40 y/o. Next, we found a significant statistical difference in serum-PSAP levels among normal adult males (n⫽ 58; ⬎40 y/o) and patients with primary or metastatic hormone-refractory PCa (HRPCa; p⫽0.0001). Compared with the normal group, serum-PSAP levels decreased in patients with primary PCa (n⫽82), but significantly increased in those with metastatic and HRPCa (n⫽29) which indicated a direct correlation between serum-PSAP levels and disease progression (p⬍0.0001; Kruskal-Wallis Test, confidence interval 95%). CONCLUSIONS: Serum-PSAP might prove to be a useful and novel biomarker for both primary and metastatic PCa. Source of Funding: Louisiana Cancer Research Consortium (LCRC-LSUHSC to S.K.), NIH/NCRR (1P20 RR021970; to A. Ochoa/S.K.), NIH (1R01 MD005824-01 to S.K.), North West SPORE (R.V.L.), LSUHSC and TULANE University Clinical and Translational Research Education and Commercialization Project (CTRECP-070 to S.K.)

2335 SOLUBLE GP130 PROMOTES PROSTATE CANCER INVASION AND PROGRESSION IN AN IL-6 INDEPENDENT FASHION Shahrokh Shariat, Thomas Chromecki*, New York, NY; Julia Hoefer, Innsbruck, Austria; Christopher Barbieri, Douglas Scherr, New York, NY; Pierre Karakiewicz, Montreal, Canada; Claus Roehrborn, Dallas, TX; Francesco Montorsi, Milan, Italy; Zoran Culig, Ilaria Cavarretta, Innsbruck, Austria INTRODUCTION AND OBJECTIVES: Soluble gp130 (sgp130) is a regulator of the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex signaling which promotes prostate cancer metastasis. We examined the association of sgp130 with prostate cancer invasiveness, differentiation, progression, and prognosis. METHODS: Experimental Design: Plasma levels of sgp130, IL-6, and sIL-6R were measured preoperatively (n⫽423) and postoperatively (n⫽206) using enzyme immunoassays in patients treated with radical prostatectomy for clinically localized prostate cancer. We also performed in vitro invasion assays on prostate cancer cells treated with sgp130 and IL-6, and used Western analysis to examine changes in E-cadherin levels. RESULTS: Higher pre-operative plasma sgp130 levels were significantly associated with higher biopsy and pathologic Gleason sum, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, and biochemical recurrence after radical prostatectomy. Post-operative sgp130 levels were 18% lower than pre-operative levels (p⫽0.037). Sgp130 levels were weakly correlated with preoperative

Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011

plasma IL-6 and sIL-6R levels. In vitro, sgp130 alone was able to increase the invasiveness of androgen-responsive prostate cancer cell lines. Sgp130 was also able to prevent E-Cadherin’s inhibition of IL-6/sIL-6R complex activity. CONCLUSIONS: In vitro and in vivo data suggest that sgp130 plays a role in prostate cancer invasion. Higher plasma sgp130 levels are associated with features of biologically aggressive prostate cancer as well as progression. The decrease in postoperative plasma sgp130 after surgery suggest that the higher blood levels of sgp130 are primarily produced by tumor cells in the primary prostate cancer. Sgp130 could serve as a target for therapy and be integrated into prognostic biomarker panels for clinical decision-making. Further research is warranted. Source of Funding: None

2336 EXPRESSION OF SEMINAL PLASMA PROTEINS IN PROSTATE CANCER: PROGNOSTIC IMPLICATIONS AFTER RADICAL PROSTATECTOMY Koji Izumi*, Anastasia Canacci, Yichun Zheng, Jennifer Gordetsky, Jorge Yao, Hiroshi Miyamoto, Rochester, NY INTRODUCTION AND OBJECTIVES: Seminal plasma proteins, semenogelins I (SgI) and II (SgII), have been shown to play a critical role in semen clotting and subsequent liquefaction in the presence of zinc and prostate-specific antigen (PSA). However, little is known about the role of semenogelins in human malignancies, including prostate cancer. METHODS: We investigated the expression of semenogelins in four human prostate cancer cell lines by reverse transcription-polymerase chain reaction and western blotting as well as in 70 radical prostatectomy specimens by immunohistochemistry. We then evaluated the associations between the expression of semenogelins and clinicopathologic features available for our patient cohort. Effects of semenogelin overexpression on prostate cancer cell proliferation were also assessed. RESULTS: mRNA and protein signals for SgI and SgII were detected in androgen sensitive LNCaP cells cultured in the presence of 100 ␮M zinc, but not in the other lines, including androgen receptor (AR)-positive CWR22Rv1 cells and AR-negative PC-3 and DU145 cells. Transfection of SgI/SgII increased/decreased cell growth of CWR22Rv1 in the presence of zinc, whereas it showed marginal effects in PC-3 and DU145. Immunohistochemical studies on prostatectomy specimens then showed that SgI and SgII stain positively in 55 (79%) and 31 (44%) cancer tissues, respectively, which was significantly higher than in corresponding benign tissues [SgI-positive in 13 (19%) cases (p⬍0.0001) and SgII-positive in 15 (21%) cases (p⫽0.0066)]. Of the 55 SgI-positive tumors, 28 (51%) were also SgIIpositive, whereas 28 (90%) of 31 SgII-positive tumors were SgI-positive. Among the histopathological parameters analyzed, there was an inverse association only between Gleason score (GS) and SgII expression (GSⱕ7 vs. GSⱖ8: p⫽0.0150; GS7 vs. GSⱖ8: p⫽0.0111; GSⱕ6 vs. GSⱖ8: p⫽0.0674). Kaplan-Meier and log-rank tests further revealed that patients with SgI-positive/SgII-negative tumor have the highest risk for biochemical (PSA) recurrence (p⫽0.0242), although the expression status of either SgI alone (p⫽0.5409) or SgII alone (p⫽0.2378) was not strongly correlated with recurrence. CONCLUSIONS: Our results suggest the involvement of semenogelins in prostate cancer and their prognostic values in predicting cancer progression after radical prostatectomy. SgI and SgII may have contradictory effects on prostate cancer progression. Source of Funding: None