Cyclooxygenase-2 expression correlates with local chronic inflammation and tumor neovascularization in human prostate cancer.
OBJECTIVE
Chronic inflammation is linked to the development of cancer in several organs, including the prostate. Up-regulated cyclooxygenase-2 (COX-2) may play a role in influencing cell proliferation, differentiation, apoptosis, or angiogenesis. This study aimed to derive data from human prostate cancer to investigate whether chronic inflammation and angiogenesis were correlated with the expression of COX-2.


METHODS
In this study, we did double-immunohistochemical analysis of a set of 43 human prostate cancer for COX-2 expression and the correlation with T-lymphocyte and macrophage densities and CD31-marked microvessel density (MVD) in situ.


RESULTS
COX-2 positive staining was detected in 40/43 cancer samples with the very heterogeneous expression. Elevated COX-2 expression was associated with high Gleason score (P = 0.002). Foci of chronic inflammation were found in all 43 samples. COX-2-positive areas were noted with high T-lymphocyte and macrophage densities than COX-2-negative tumor areas (P < 0.0001 and P = 0.001, respectively). MVD were also found higher in COX-2-positive areas than in COX-2-negative tumor areas (P = 0.001).


CONCLUSIONS
This study shows a novel relationship between COX-2 expression and the local chronic inflammation within prostate cancer and the increased angiogenesis. It is likely that the proinflammatory cytokines, released by T-lymphocytes and macrophages, up-regulate COX-2 in adjacent tumor cells and stimulate the angiogenesis in stromal tissues. These findings suggest that COX-2 may be an effective therapeutic target in prostate cancer treatment.
Wang
Wanzhong
W
Department of Urology, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
Bergh
Anders
A
Damber
Jan-Erik
JE
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology; D015854:Up-Regulation; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051546:Cyclooxygenase 2; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496540:PTGS2 protein, human