Expression of protease activated receptor-2 related to angiogenesis in tumor advancement of uterine endometrial cancers.

Protease activated receptor-2 (PAR-2) is the second member of a novel family of G-protein coupled seven-transmembrane domain receptors. PAR-2 has been reported to be expressed in various tumors and play a vital role in the regulation of cancer cell growth. The purpose of this study was to clarify the roles of PAR-2 in the angiogenic pathway in uterine endometrial cancers. PAR-2 expression was analyzed in 61 uterine endometrial cancer and 15 normal endometrium tissue specimens. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT-PCR, respectively. Microvessel counts were determined by immunohistochemistry for CD31 and factor VIII-related antigen. The localization of PAR-2 was dominant in the cancer cells of endometrial cancer tissues of all cases studied. PAR-2 histoscores highly correlated with PAR-2 mRNA levels in the same tissues (r=0.87, p<0.001). PAR-2 histoscores and mRNA levels both significantly increased in uterine endometrial cancers with clinical stages (I<II<III, p<0.001), dedifferentiation (G1<G2<G3, p<0.001) and myometrial invasion (A<B, p<0.001; B<C, p<0.05) in comparison to normal endometria. There were significant correlations between PAR-2 histoscores and mRNA levels with microvessel counts in uterine endometrial cancers. PAR-2 was upregulated during uterine endometrial cancer progression with dedifferentiation and myometrial invasion. Therefore, PAR-2 might work on tumor advancement of uterine endometrial cancers via angiogenic activity.