Furin Expression in Seminal Vesicle. Any Impact on Prostate Cancer Development?
Yulan Gong, Claudio Torres, Christian Sell, Alessandro Bitto, Jian Fu, Andres J Klein-Szanto, Fernando U Garcia. Drexel University College of Medicine, Philadelphia, PA; Fox Chase Cancer Center, Philadelphia, PA
Background: Prostate and seminal vesicle (SV) are organs that are anatomically and functionally related. However, while prostate cancer (PCa) is very common in older men, the SV rarely develops cancer. The fact that two closely related organs have such different cancer rates offers an opportunity to study potential underlying molecular interactions that determine cancer development exclusively in prostate. There is little information characterizing the SV in terms of proliferation and senescence and the possible impact on PCa development. Furin, a calcium dependent serine proteinase, has been shown to be over expressed in a variety of cancer cells and selectively activate IGF-1 and IGF-1 receptor by limited protein digestion. We propose to study the expression of Furin and to characterize senescence in SV on different age groups using two well-established markers P21 and P16.
Design: Immunofluorescence for P21 and P16 and immunohistochemistry (IHC) for Furin were evaluated in SV of two different age groups (younger < 60 and older ≥60 years) (n=9 in each group). Tissue microarrays from 23 de-identified radical prostatectomy specimens with duplicate cores from benign glands, PCa and SV were constructed. Furin, PTEN, P53 and Ki-67 expression levels were evaluated by IHC using image analysis. Both P21 and P16 were quantified manually. Expression was compared using t-test.
Results: P16 and P21 expression levels are increased significantly during SV aging. P16 is expressed in 19.2% of epithelial cells in the younger group and 42.4% in the older group (p<0.05). P21 is expressed in 13.3% of epithelial cells and 49.1% in the older group (p<0.05). Furin is highly expressed in the luminal cells of SV and SV fluid and there is increased expression during aging, Immunoscore (IS): 193.8 in younger group and 233.9 in the older group, p<0.05). However, within the prostate, Furin expression is highest in atrophic glands, followed by high-grade prostatic intraepithelial neoplasm (HGPIN) and PCa. PTEN expression is low in PCa cells, IS: 42.8 when compare to benign glands, IS: 62.3 (p<0.05) and SV, IS: 75.4 (p<0.05). Ki-67 has an opposite expression pattern. P53 expression is low in all areas.
Conclusions: 1) SV senescent cell population increases with age. 2) Furin expression is increased during aging in SV. 3) Furin is present in prostatic atrophy and HGPIN. 4) We propose that increases in the population of senescent cells within SV during aging, changes their secretory pattern by increasing Furin expression.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 210, Wednesday Morning