Lower expression of cyclooxygenase-2: is it associated with the development of borderline ovarian tumors?

Epithelial ovarian neoplasms can be divided into two major categories on the basis of their pathological and clinical behaviors: invasive ovarian tumors and borderline ovarian tumors. However, neither the etiology nor the pathogenesis of the borderline and invasive epithelial ovarian carcinomas has been understood completely. Borderline tumors are clearly more favaroble in terms of survival. The same pathological types can be seen both in borderline and invasive tumors. However; it is not clear if both diseases is a continuum of the same entity or are independent clinical entities. On the other hand, several in vivo and in vitro studies have demonstrated that overexpression of the cyclooxygenase-2 (COX-2) may have an important role in the development and the aggressive clinical behaviors of different malignancies. Furthermore, some recent studies have also revealed the overexpression of COX-2 in invasive epithelial ovarian carcinomas. In this manuscript, we propose that lower expressions of COX-2 may have a role in the development of borderline ovarian neoplasias, whereas higher levels have a role in the invasive epithelial ovarian cancers and this may be the basis for the clinical difference of both entities. To test this hypothesis; genetic, pathologic and epidemiologic studies may be performed. Patients with borderline tumors should be compared with the invasive counterparts in terms of COX mutations and expressions. Also, epidemiologic studies may reveal the role of COX inhibitors in the ovarian carcinogenesis. If this hypothesis is proven to be true, this may direct the clinicians to use prophylactic NSAIDs with or without combined oral contraceptives especially in high risk patients. Also, this hypothesis may enlight a new gene therapy targeting COX-2 gene in high risk patients for the development of EOC.