[882] The Expression of the Androgen Receptor Coactivator P44 in Proliferative Inflammatory Atrophy

OE Kabiawu, J Melamed, M Yu, J Wang, S Jain, N Aladhamy, Z Wang, P Lee. New York University School of Medicine, New York, NY

Background: Proliferative inflammatory atrophy (PIA) in prostate consists of atrophic glandular foci with proliferative glandular epithelium and associated inflammation. It has been hypothesized that PIA may be linked to prostate carcinogenesis. Importantly, PIA lesions share a number of molecular and genetic changes with high grade prostatic intraepithelial neoplasia and carcinoma, including chromosome 8 abnormalities, p53 mutations, an increased level of Bcl-2 protein and down-regulation of p27. A functional androgen-signaling pathway is essential for the development and progression of prostate cancer. Various AR cofactors, including p44, have been shown to regulate androgen receptor (AR) activation. We have previously shown that nuclear p44 maintains prostatic epithelial cells in a growth-arrest state, conversely, the cytoplasmic localization of p44 results in epithelial cell proliferation. In this study, we examined the expression of AR and its coactivator p44 in PIA.
Design: Cases (n = 44) containing PIA, benign and carcinoma foci were identified from a radical prostatectomy series. Immunohistochemistry using AR and p44 antibodies were performed on paraffin embedded tissue sections. Areas satisfying criteria for PIA [Working group classification of focal prostate atrophy lesions; De Marzo et al 2006] were evaluated together with carcinoma and non-neoplastic foci. Immunoreactivity for p44 and AR was scored separately using nuclear and cytoplasmic proportion-intensity score. The Applied Wilcoxon and Shapiro-Wilk Normality tests were performed for statistical significance.
Results: The mean value for the PIA nuclei score = 4.625, and the cytoplasmic score = 4.875. p44 expression in PIA showed an increase in nuclei staining as compared with carcinoma foci (p= 0.02), and a decrease from benign prostate tissue (p < 0.01). Also, p44 cytoplasmic expression was decreased in PIA as compared with the baseline carcinoma foci control (p < 0.01), and increased compared with benign prostate tissue (p < 0.01). The trend in staining shows a progressive increase in nuclear staining and decrease in cytoplasmic staining in benign prostate (p < 0.01), PIA and carcinoma respectively (p < 0.01). Androgen receptor, on the other hand, is expressed strongly and uniformly in all three categories.
Conclusions: The above findings of nuclear and cytoplasmic expression of p44 at an intermediate level between benign and carcinoma provides additional support for PIA as a putative premalignant lesion.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 122, Wednesday Afternoon

 

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