Decreased Stromal Androgen Receptor Expression in African-Americans with Prostate Cancer
Christopher S Hale, Max X Kong, Qinghu Ren, Yirong Li, Stephanie Krauter, Luis Chiriboga, Iman Osman, Victor Reuter, Rosemary Wieczorek, Jonathan Melamed, Peng Lee. NYU Langone Medical Center, New York; Memorial-Sloan Kettering Cancer Center, New York
Background: African-Americans (AA) have prostate cancer (PCa) mortality 2-3 times that of Caucasians (CA). The basis for this disparity is not fully understood; however, data suggest molecular changes in different ethnicities are responsible. Expression of regulatory molecules, such as epithelial growth factor receptor, has been found to vary significantly between racial groups. Androgen receptor (AR) expression is critical for PCa tumorigenesis and progression. The relationship between race and stromal androgen receptor expression has not previously been analyzed.
Design: Immunohistochemical double staining for AR and smooth muscle actin was performed on a tissue microarray containing 148 cases of prostate cancer (known race n=31 for AA and n=63 for CA). AR positivity in fibroblasts was quantified as a percentage. The histologic pattern of smooth muscle and fibroblasts surrounding benign and cancerous areas was evaluated semiquantitatively.
Results: Earlier in vitro co-culture experiments with cancer epithelial (PC3 and LNCaP) and stromal (either AR positive or AR negative) cells have indicated that stromal AR inhibits PCa growth. Moreover, stromal AR has been found to be decreased in PCa. In the present study we find stromal AR expression to be 75% lower in cancer, irrespective of race (16.4±11.5%, n=107, versus 4.7±0.8%, n=148, P < 0.0001). Among AA men with PCa, the percent of AR-positive stromal cells is 83% lower (1.5±0.5%, n=31) than in CA men with PCa (8.5±1.7%, n=63, P < 0.0002). As additional evidence of stromal-epithelial interaction, we observe immediate juxtaposition of continuous smooth muscle fibers around a high percentage of benign prostate glands (64±3.0%, n=103). Continuous smooth muscle is less prevalent around cancerous glands (46±2.4%, n=141, P < 0.0001), with smooth muscle admixed with an intervening fibroblastic component. Lack of continuous and immediate juxtaposition of smooth muscle fibers is more pronounced in AA men with PCa (39±4.4%, n=47) relative to CA men with PCa (54±5%, n=39, P < 0.0229).
Conclusions: Stromal-epithelial interaction is an important factor in progression of PCa. Decreased stromal AR expression may contribute to African-Americans' poorer clinical outcomes. This is supported by evidence that stromal AR inhibits prostate cancer growth. In the era of personalized medicine, understanding differences in PCa biology will aid selection of more targeted therapies.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 147, Monday Morning