Poster, Podium & Video Sessions
Presentation Authors: Shardul Soni*, Michael Glover, Qinghu Ren, Gregory MacLennan, Pingfu Fu, Sanjay Gupta, Cleveland, OH
Introduction: The relationship between inflammation and prostate cancer has not been established, although chronic inflammation has frequently been identified in prostate biopsies, radical prostatectomy specimens and tissue resected for treatment of benign prostatic hyperplasia. In the peripheral zone of the prostate, sometimes adjacent to foci of high-grade PIN and cancer, certain morphologic changes are often identified, which may represent active and terminal phases of chronic inflammation. These changes are designated, respectively, proliferative inflammatory atrophy (PIA) and post atrophic hyperplasia (PAH), and their morphology is well documented in pathologic literature. In our previous studies, we have identified chronic inflammation as a putative contributor to neoplastic progression in prostate epithelial cells, and hypothesized that its adverse effects were related to an increase in Bcl2, a survival protein involved in cell survival and carcinogenesis. We hypothesize that changes in the stromal microenvironment, characterized by infiltration of immune cells, with generation of reactive oxygen and nitrogen species, can induce oxidative stress in the surrounding proliferating epithelium and cause permanent genomic alterations. Here we focused on several key proteins involved in the inflammatory process, COX2 and iNOS; cell survival, Bcl2 and GSTPπ; and evaluated expression of alpha-methylacyl coenzyme A racemase (AMACR) and basal cell-specific markers 34βE12 and/or p63 to evaluate possible neoplastic alterations in epithelial cells in an inflammatory environment.
Methods: We evaluated 16 prostate core needle biopsy specimens that exhibited the presence of chronic inflammation as well as PIA and PAH lesions. Immunohistochemical staining for P63/34βE12/AMACR cocktail, iNOS, COX2, GSTπ, and Bcl2 was performed in each set of biopsies.
Results: The integrity of the basal layer was maintained in the area of chronic inflammation with high to moderate expression of p63 in 72% of these cells. Approximately 68% of luminal cells expressed high to moderate levels of iNOS and COX-2, whereas 55% of these cells express modest levels of GSTπ and Bcl2. We found that basal cells near areas of chronic inflammation in the PIA lesions exhibit high AMACR expression and weak to no p63 expression. Loss of p63 and increased AMACR expression in the basal cells was associated with increased expression of the inflammatory markers COX2 and iNOS, as well as loss in pro-survival signal GSTP1 and Bcl2 in the adjacent luminal cells. These neoplastic alterations were observed in 6/16 (38%) of the needle biopsy specimens.
Conclusions: Our findings suggest that basal cells undergo alterations in a setting of chronic inflammation. This is important because basal cells are considered to be progenitor cells capable of differentiating into secretory luminal cells, but under the influence of chronic inflammation, they may instead transform into the neoplastic cells that characterize high grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma.
Source Of Funding: Department of Defense grant W81XWH-15-1-0558, USPHS R21CA193080, R03CA186179 and VA Merit Review 1I01BX002494 to SG.
Case Western Reserve University
Friday, May 12
1:00 PM – 3:00 PM