Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis.

摘要: Proliferation in the setting of longstanding chronic inflammation appears to predispose carcinoma liver, large bowel, urinary bladder, and gastric mucosa. Focal prostatic atrophy, which is associated with inflammation, highly proliferative (Ruska et al, Am J Surg Pathol 1998, 22:1073–1077); thus focus this study was more fully characterize phenotype atrophic cells assess feasibility proposal that they may be targets neoplastic transformation. The π-class glutathione S-transferase (GSTP1), a carcinogen-detoxifying enzyme, not expressed >90% prostate carcinomas (CaPs). GSTP1 promoter hypermethylation, permanently silence transcription, most frequently detected genomic alteration CaP (Lee Proc Natl Acad Sci USA 1994, 91:11733–11737; cases). In high-grade intraepithelial neoplasia (PIN), present at least 70% cases (Brooks Cancer Epidemiol Biomarkers Prev, 7:531–536). Although normal-appearing secretory rarely express GSTP1, remain capable expression, inasmuch as hypermethylation normal prostate. Fifty-five lesions from paraffin-embedded prostatectomy specimens (n = 42) were stained for using immunohistochemistry. Adjacent sections p27Kip1, Ki-67, androgen receptor (AR), prostate-specific antigen (PSA), acid phosphatase (PSAP), Bcl-2, basal cell-specific cytokeratins (34βE12). With epithelium internal standard, staining scored each marker epithelium. showed two cell types, positive 34βE12, secretory-type weakly negative 34βE12. All elevated levels Bcl-2 many cells. had an index proliferation Ki-67 layer decreased expression finding reminiscent PIN (De Marzo 153:911–919). Consistent partial differentiation, luminal weak moderate proteins PSA PSAP. Because all are hyperproliferative, have distinct morphological appearance recognized we suggest term “proliferative inflammatory atrophy” (PIA). Elevated reflect its inducible nature cells, possibly response increased electrophile or oxidant stress. responsible very low apoptotic rate PIA consistent conclusion regenerative lesion. We discuss our integrate atrophy hypotheses carcinogenesis by suggesting give rise either directly, previously postulated, indirectly first developing into PIN.