The Association between Apoptosis and Androgen Receptor in Benign Prostatic Hyperplasia, Prostatic Intraepithelial Neoplasia and Prostate Carcinoma*
Sema Bircan, Sirin Baspinar, Kemal Kursat Bozkurt, Korkut Bozkurt, Fatma Nilgun Kapucuoglu, Alim Kosar. Suleyman Demirel University School of Medicine, Isparta, Turkey
Background: The aim of this study was to investigate the relationship of apoptosis-regulating genes and Androgen Receptor (AR) expression with histopathological features in benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate adenocarcinomas (PC).
Design: The study included 30 BPH, 40 HGPIN and 114 primer PCs including 82 radical prostatectomy. They were re-reviewed for Gleason scoring and pT staging. HGPINs were obtained from the specimens of the cases with or without PC. Immunohistochemistry were performed on the tissue microarray (TMA) sections for FasLigand, caspase-3, APAF-1, TRADD, NF-kB, PTEN, Bcl-2, Bax, AR, and evaluated based on the percentage of the staining cells.
Results: The mean expressions in BPH, HGPIN, PC for FasLigand were 5.91, 17.17, 4.10; for Caspase-3 were 7.74, 96.50, 62.57; for APAF-1 were 0.00, 57.12, 33.71; for TRADD were 60.33, 89.87, 88.14; for NF-kB were 99.66, 97.62, 90.15; for PTEN were 90, 1.20, 49.39; for Bcl-2 were 0.08, 97.75, 79.59; for Bax were 0.13, 8.55, 0.92; for AR were 71.98, 33.58, 36.77. There were significant differences in the mean expressions of all markers examined between the groups by Anova test (p<0.05). Significant correlations were found between NF-kB and Bax (p<0.0001,r=-0.947), and TRADD and PTEN, AR (p=0.018,r=0.435;p=0.019,r=0.434) in BPH, and PTEN and AR (p=0.001,r=0.490) in HGPIN. In PCs, PTEN expression positively correlated with FasLigand, NF-kB and Bax (p=0.040,r=0.210;p=0.009,r=0.256; p=0.014,r=0.247), and Bcl-2 also inversely correlated with PTEN, Bax (p<0.0001,r=-0.546;p=0.018,r=-0.237). Caspase-3 expression showed positively correlation with APAF-1, TRADD, NF-kB and AR (p=0.019,r=0.237;p<0.0001,r=0.402;p=0.003,r=0.297;p<0.0001,r=0.501, respectively). TRADD expression related with NF-kB, PTEN, APAF-1 and AR(p<0.0001,r=0.583;p=0.003,r=0.298;p=0.007,r=0.261;p=0.002,r=0.303). Gleason score of the PCs positively correlated with caspase-3, PTEN, Bax and AR (p<0.05), and pT stages inversely related with PTEN (p=0.034,r=0.240).
Conclusions: According to the results, different type of apoptosis-related markers are involved during the tumorogenesis from BPH to HGPIN and PC. The overexpression of Caspase-3, Bcl-2, APAF-1 and TRADD and downregulation of PTEN and AR seem to be related with increasing malignant transformation.
*This study was supported by the Turkish Association for Cancer Research and Control, Terry Fox Foundation.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 174, Tuesday Afternoon