Tumor-associated stromal cells expressing E-prostanoid 2 or 3 receptors in prostate cancer: correlation with tumor aggressiveness and outcome by angiogenesis and lymphangiogenesis.

OBJECTIVE To clarify the detailed pathologic roles of prostaglandin E-2 in prostate cancer tissues, the present study investigated the clinical significance and prognostic roles of the density of tumor-associated stromal cells expressing specific receptors for prostaglandin E-2, termed "E-prostanoid (EP)1-4 receptors (EP1R-4Rs)." METHODS The expression of each receptor was immunohistochemically examined in 114 formalin-fixed biopsy specimens. Correlations with clinicopathologic features were investigated in these specimens. Angiogenesis and lymphangiogenesis were measured by the percentage of CD34-stained vessels (microvessel density) and D2-40-stained vessels (lymph vessel density). The relationships between the density of each EPR-stained cells and the microvessel density or lymph vessel density were evaluated in 62 prostate cancer tissues obtained by radical surgery for more detailed analysis in a wider area of prostate cancer tissue. RESULTS The density of tumor-associated cells with EP2R expression was positively associated with the N (P < .001) and M ( P = .002) stages. Similarly, EP3R-positive stromal cell density was significantly associated with the N (P = .033) and M (P = .026) stages. The density of EP2R- and EP3R-stained cells correlated with the microvessel density (r = 0.42, P < .001) and lymph vessel density (r = 0.36, P = .012), respectively. A greater density of EP2R-stained cells was recognized as an independent predictor of progression (hazard ratio 7.26, P = .002) on multivariate analysis. CONCLUSION EP2R- and EP3R-stained cells might play important roles in tumor progression, angiogenesis, and lymphangiogenesis in prostate cancer. The density of EP2R-stained stromal cells could offer a useful predictor of biochemical recurrence after radical surgery. UROLOGY 81: 136-142, 2013. (c) 2013 Elsevier Inc.