Significance Of COX-2 And VEGF Expression In Pituitary Adenomas

Background: Prostaglandin endoperoxide synthases, also known as the cyclooxygenase enzymes, COX-1 and COX-2, are the key enzymes which can convert arachidonic acid into prostaglandins. In recent years, epidemiologic investigations, animal experiments and cytological experiments suggested that COX-2 had relation with the development and progression of various epithelial tumors and could become target molecules to prevent and treat tumors. VEGF, an important angiogenesis stimulator, can promote the procedure of angiogenesis and thus enhance the development and progression of tumors. Studying the expression of COX-2 and VEGF in pituitary adenomas is significant and could provide a novel approach for prevention and treatment of pituitary adenomas.Objective: This study aims to investigate the relationship between the expression of COX-2 and VEGF and the biological behavior of pituitary adenomas by examining their expression in pituitary adenomas as well as in normal hypophysias, and to investigate the correlation of the expression of COX-2 and VEGF so as to explore their effects in the angiogenesis of pituitary adenomas and to provide a novel approach for prevention and therapy of pituitary adenomas.Methods: 120 paraffin samples of pituitary adenomas were collected as experiment group and 7 pieces of normal pituitary tissues as control group. The expression of COX-2 and VEGF protein was examined by immunohistochemical staining. The intensity of immunohistological staining was semiquantitatively scored on thebasis of cell- counting and immunohistological markers observed by microscopes as well as clinical and pathological data.Results: 1. In 120 samples with pituitary adenomas, COX-2 protein expression was strongly positive in 20.0% samples ( 24 cases ), positive in 72.5% samples ( 87 cases )and negative in 7.5% samples ( 9 cases ). However, COX-2 protein expression was negative in all 7 cases of normal pituitary. No correlation was observed between the expression of COX-2 and patients age, gender, sizes of tumors as well as pathological types. The intensity of COX-2 expression was associated with the invasive ability of tumors( P <0. 01 ). 2. In 120 samples with pituitary adenomas, 46.7% samples ( 56 cases ) showed strongly positive expression of VEGF protein, 51.6% samples ( 62 cases ) positive and 1.7% samples ( 2 cases ) negative. However, no VEGF protein expression was observed in any of the 7 cases of normal pituitary. No correlation manifested between the expression of VEGF and patients age, gender, size of tumor as well as pathological types. The intensity of VEGF expression was significantly stronger in invasive pituitary adenomas than in localized ones( P<0. 01 ). 3. The expression of COX-2 and VEGF was significantly correlated in pituitary adenomas( P<0. 01).Conclusion: The enhanced expression of COX-2 in pituitary adenomas suggested that COX-2 was involved in the development and progression of adenomas. The higher expression of COX-2 in invasive pituitary adenomas than in localized ones suggested that the expression of COX-2 contributed to the invasive ability of adenomas. Similarly, the higher expression of VEGF in invasive pituitary adenomas than in localized ones suggested that the expression of VEGF also contributed to the increase of invasive ability ofadenomas. The distinct correlation between the expression of COX-2 and VEGF suggested that COX-2 might participate in the regulation of angiogenesis in pituitary adenomas. So controlling the activity of COX-2 by NSAIDs may inhibit the angiogenesis process in pituitary adenomas and become a novel approach for drug therapy of pituitary adenomas.