Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium.
BACKGROUND
Chronic inflammation has been suggested to be linked to the development and progression of prostate cancer. An inflammatory microenvironment may support the development of malignancy by upregulation of proinflammatory cytokines and cyclooxygenase-2 (COX-2). Recent studies have suggested that COX-2 is upregulated in cancer and in proliferative inflammatory atrophy (PIA) of the prostate.


METHODS
Immunohistochemistry (IHC) was used to investigate the expression of COX-2 in prostate epithelium. The relationships between COX-2 expression and inflammatory cells, proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67), and apoptosis (Bcl-2) were studied in 45 BPH samples.


RESULTS
COX-2 expression was detected in prostate luminal epithelial cells in all 45 samples studied. The overall percentage of COX-2 positive glands was 7.5%, distributed as 0.2% positive glands in normal prostate tissue, 25.7% in postatrophic hyperplasia (PAH), and 11.9% in simple atrophy (SA). The highest proliferation index was found in COX-2 positive stained epithelium. COX-2 expression was associated with Bcl-2 immunostaining in atrophic lesions (P < 0.0001). T lymphocytes and macrophages were the predominant inflammatory cells related to the COX-2 expression in prostate epithelium.


CONCLUSIONS
The data demonstrate that T lymphocytes and macrophages appeared to play an important role in the induction of COX-2 expression in prostate epithelium, which was associated with increased cell proliferation and possibly, due to overexpression of Bcl-2, apoptotic resistance. This suggests that pro-inflammatory cytokines released by adjacent inflammatory cells may induce COX-2 in the epithelial cells in prostate atrophic lesions. In addition, COX-2 expressing cells may be involved in the pathogenesis of prostate cancer.
Wang
Wanzhong
W
Department of Urology, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
Bergh
Anders
A
Damber
Jan-Erik
JE
D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000502:physiology; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases