Expression of protease activated receptor-2 (PAR-2) in gastric cancer

Background and Objectives: Recently, the four-kind cloning of the protease-activated receptor (PAR) had been carried out. PAR-2 is activated by trypsin and it is supposed that PAR-2 participated in proliferation of the endothelial cell or in neovascularization. We considered whether the expression of PAR-2 has relevance to progression in gastric cancer. Methods: Immunohistochemical study by the envision method was carried out on 183 samples of gastric cancer in the first department of surgery, University of Fukui, using anti-PAR-2 mouse monoclonal antibody and on 95 samples of them that were pointed out advanced gastric cancers by pathological diagnosis using anti-trypsin rabbit polyclonal antibody. Tissues, which were stained more than 20% of the tumor cells, were classified as PAR-2 protein-positive. Correlation with immunostainings and clinicopathological factors was analyzed statistically. Results: There were 77 (42.1 %) carcinomas positive for PAR-2 expression. The PAR-2 expression was intensely strong on the cell membrane of primary cancer tissues. The expression of PAR-2 correlated with the depth of wall invasion, lymphatic invasion, venous invasion, and liver metastasis. The patients with PAR-2 expression-positive tumors had a significant poorer prognosis than those with expression-negative tumors. Univariate analyses identified PAR-2 expression as negative predictors. Multivariate analyses indicated that PAR-2 expression was not an independent factor. A positive reaction for trypsin was obtained in 45 (47.4%) patients. We found a significant correlation between PAR-2 immunostaining and trypsin immunostaining. Conclusion: The results of this study lead us to believe that expression of PAR-2 is concerned with progression of gastric cancer.