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Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer

Authors' Affiliations: ¹ Department of Urology, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden and ² Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden

Requests for reprints: Jan-Erik Damber, Department of Urology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Phone: 46-31-342-3977; Fax: 46-31-416347; E-mail: jan-erik.damber{at}urology.gu.se.

Purpose: 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.

Experimental Design: 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 proinflmmatory 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.

Key Words: COX-2 • prostate cancer • inflammation

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