Oxidative Damage Sensor in Atrophy and Adenocarcinoma in the Prostate.
Ashish P Mogal, Mark A Watson, Peter A Humphrey. Washington University School of Medicine, St. Louis, MO
Background: Chronic inflammation of long standing duration is thought to play a significant role in the pathogenesis of cancer in several organs and has been implicated as being potentially important in prostate cancer development. Proliferative inflammatory atrophy (PIA) has been proposed as a potential precursor lesion for prostate cancer. However, the precise molecular abnormalities in PIA vs carcinoma have not been fully defined. We have previously analyzed the molecular variability and differential genetic signatures within normal, atrophic, PIN and invasive carcinoma subgroups by microarray analysis. Here, we utilized an immunohistochemistry (IHC) approach to confirm expression of a biologically relevant 21 kDa protein (21kDaP), identified by differential microarray expression analysis, that plays a protective role against oxidative damage and thus, may have implications in the pathogenesis of the putative PIA to carcinoma pathway.
Design: Fifty radical prostatectomies were utilized, based on the presence of benign epithelium, atrophy, PIN, and invasive carcinoma in the same case. H&E sections were reviewed and peripheral zone non-atrophic benign epithelium (NABE, n=93), atrophy (n=93), PIN (n=34) and invasive carcinoma (n=61) lesions were selected. Different morphological subtypes of atrophy were included: simple (SA=68), simple with cyst formation (SACF=32), post atrophic hyperplasia (PAH=21), partial (P=4) and PIA (54). IHC was performed on sections from paraffin embedded tissue blocks for 21kDaP. IHC results were evaluated for proportion reactivity (% glands with positive staining), cytoplasmic vs nuclear reactivity and intensity (1+, 2+, 3+) of 21kDaP staining.
Results: 21kDaP expression was detected as follows: 92/93 atrophy, 23/61 cancer, 3/34 PIN, 57/93 NABE. All subtypes of atrophy showed heterogeneous reactivity for 21kDaP. The mean reactivity for atrophy lesions was 60% while cancer / PIN lesions showed 20% reactivity. 87/92 (94%) atrophy lesions showed strong (2+, 3+) granular cytoplasmic reactivity. By contrast, 13/23 (56%) cancer cases showed diffuse mild (1+) nuclear reactivity. NABE showed variable (1+) nuclear and cytoplasmic reactivity.
Conclusions: 21kDaP protein expression was elevated in almost all atrophy cases irrespective of morphological subtype, compared to non-atrophic benign epithelium. Our results suggest that molecular perturbations secondary to oxidative tissue damage may play a significant role in a relationship between PIA and carcinoma. Further studies are warranted to explore other genes involved in this damage process and putative progression pathway.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 143, Monday Afternoon