The pattern of Protease Activated Receptor 1 (PAR1) expression in endometrial carcinoma

Objective. Protease Activated Receptors (PARs) form a family of G-protein-coupled proteins uniquely activated by proteolytic cleavage. While the role of either soluble or matrix-immobilized protease in tumor invasion is well established, the part of cell surface PARs is beginning to emerge. We sought to investigate the expression pattern of Protease Activated Receptor 1 (hPar1) in endometrial carcinoma, the most common type of gynecological malignancy. Methods. Tissue biopsy specimens taken from seventy-four formalin-fixed, paraffin-embedded endometrial tissue blocks were obtained from archival material. Analysis of PARI expression was evaluated by riboprobe in situ hybridization for detection of RNA and immunohistochemistry techniques for localization of protein. Histological scoring was performed. Results. The levels of hPar1 mRNA and protein were high and abundant in high-grade endometrial carcinoma, regardless of the histological subtype. In contrast, no hPar1 was detected in endometrial epithelia with conserved glandular structure represented by normal, hyperplastic or low-grade carcinomas. Conclusions. PARI over-expression is selectively confined to the highly aggressive, high-grade endometrial carcinoma and absent in tissue obtained from benign endometrium or low-grade endometrial cancer. This finding highlights the significance of hPar1 gene involvement in invasive endometrial carcinoma and appoints it an attractive candidate for anti-cancer therapy. (c) 2006 Elsevier Inc. All rights reserved.