Expression of the serine protease hepsin and clinical outcome of human endometrial cancer.

Background: Hepsin is a type II transmembrane serine protease originally identified in the human liver as a cDNA clone. Hepsin was found to be significantly overexpressed in cancer samples compared to matched various tissues (e.g. prostate, renal, ovarian carcinoma). The purpose of the present study was to examine hepsin expression and to evaluate its clinicopathological significance in endometrial cancer. Patients and Methods: Hepsin expression was examined by immunohistochemisty in 34 cases with normal endometrium as a control, 11 cases with endometrial hyperplasia, and 128 cases with endometrioid adenocarcinoma. Results: Hepsin expression was found to be significantly higher in endometrial cancer compared to normal endometrium and endometrial hyperplasia. High levels of hepsin expression were associated with advanced stage (p<0.001), high grade (p=0.002), depth of myometrial invasion (p<0.001), cervical involvement (p=0.007), lymph node metastasis (p=0.001), lymph vascular space (LVS) involvement (p=0.006), ovarian metastasis (p=0.002), and peritoneal cytology (p=0.03) of endometrial cancer. Conclusion: These findings indicate that hepsin protein expression could be an important indication for high risk of endometrial cancer. Endometrial cancer is currently the fourth most common gynecological malignancy in Japan, with an estimated incidence of 4,046 new cases in 2003 (1). Clinical parameters such as stage of the disease, nuclear grade, histological subtype, and tumor size correlate with the outcome of the disease. Although it is a relatively common cancer, the molecular genetic factors related to the development of endometrial cancer and its prognosis have only recently begun to be investigated. It is hoped that through a better understanding of the molecular genetic alterations implicated in endometrial cancer a more complete profile of risk factors can be developed. The proposed underlying molecular mechanisms implicated in the progression of endometrial cancer include over- expression of oncogenes such as HER-2/neu and myc, and loss of tumor suppressor genes such as p53 (2-4). The serine proteases are one of the largest and most conserved multigene proteolytic families (5). These enzymes are present in a wide range of tissues and biological fluids, and have well-characterized roles in diverse cellular activities, including blood coagulation,