Aromatase,COX-2 And VEGF Expression And Significance In Endometrial Carcinoma

Objective Endometrial carcinoma is one of the common female malignant tumors. Endometrial carcinoma, cervical cancer and ovarian tumor are the three most malignant tumors in female reproductive duct. Near twenty years the outbreak rate reported is the ascending trend. Endometrial carcinoma accounts for 7% of the all female malignant tumors and 20%-30% of female procreant system malignant tumors in China. Most cancers occur in pre-and post-menopausal women and become a major disease that threatens old female lives. The etiology is still not clear today. Epidemiological survey and experiment indicate that endogenous and exogenous estrogen is the thief factor which stimulate cell proliferation in time and dose-dependent pattern.As a horomone-dependent tumor, aromatase, the enzyme system catalyzing estrogen has been highlight. Increased aromatase expression in the endometrial carcinoma was recently reported in foreign. Intratumoral estrogens could function as an autocrine growth and mitogenic factor, and could impart a growth advantage to endometrial carcinoma cells. But a better understanding of the biological significance of intratumoral aromatase in the endometrial carcinoma is still not reported, where is the localization of aromatase expression in the endometrial carcinoma, which cells in tumor tissue produce estrogens and what is the correlation between aromatase expression and clinical course or clinicopathological parameters of patients.Endometrial carcinoma is also a kind of genic disease involving the activation of tumor suppressor genes, resulting in proliferation, invasion and metastasis. COX-2 is an inducible immediate-early gene that is upregulated by cytokines, growth factorsand mitogens. More and more studies have demonstrated that COX-2 expression was aberrantly increasing in various human epithelial cancers. COX-2 overexpression in endometrial carcinoma cells can be associated with upregulating bcl-2 and apoptosis inhibition, decreased E-cadherin, increased metastatic potential, neoangiogenesis. It is necessary to research COX-2 expression in endometrial carcinoma.Tumor growth and metastasis depends on newly formed blood vessels, which sustain tumor cell viability and growth. VEGF is better factor making neoangiogenesis. It overexpresses in many malignant tumors and takes part in development and metastasis.To clarify former questions, the present study were undertaken to detect aromatase, COX-2 and VEGF expression and their association with clinic pathologic features in endometrial carcinoma, to investigate the molecular changes in endometrial carcinoma and to provide the theoretical basis and strategies for clinical biotherapy and preventions.Methods Fifth cases of normal endometrium, twenty-five endometrial hyperplasias and forty-two endometrial adenocarcinomas were enrolled from the second affiliated hospital of Zhengzhou University. All the patients were not treated by chemotherapy, radiotherapy and sex hormone therapy before operation. All the surgically resected specimens were fixed with 10% fomalin, paraffin embedden, and serially sectioned for histopathological diagnosis, immunohistochemical analysis.Immunohistochemical method (SP method) was applied to determine the protein expression of aromatase, COX-2 and VEGF. The data was analyzed by SPSS 10.0 statistical software. The x~2 test and Fisher's exact test of probabilities was used. A value of P <0.05 was considered statistically significant.Results Form normal endometrium, endometrial hyperplasia to endometrial carcinoma, the positive rates of aromatase expression were 0%, 0%, 59.5% respectively. The differences were significant between the former two groups and endomtrial carcinoma (P<0.01). There were not a direct associated between age,FIGO stage, grade and outer half myometrial invasion and aromatase immunostaining.With the lesions progressed from normal endometrium, endometrial hyperplasia to endometrial carcinoma, a increasing tendency of COX-2 expression was observed, the postive rates were 6.7%, 52.0%, 61.9% respectively. The differences were significant between hyperplasia or carcinoma and normal (P<0.01). From Gi to G2 + G3 in histological grade, the positive rates of COX-2 were 45.0% and 77.3% respectively. And the difference was significant (P<0.05). From inter half myometrial invasion to outer, the positive rates of COX-2 were 48.0% and 82.4% respectively. And the latter was higher than the former (P<0.05).The increasing tendency of VEGF expression was observed from normal endometrium, endometrial hyperplasia to endometrial carcinoma. The positive rates were 13.3%, 48.0%, 64.3% respectively. The differences were significant between hyperplasia or carcinoma and normal( P<0.05, P<0.01).The positive immunostaining rate of COX-2 in the aromatase postive group was significantly higher than in the negative group in endometrial carcinoma. The distinct concordance was observed between aromatase and COX-2 (P<0.01).The positive immunostaining rate of VEGF in the aromatase postive group was significantly higher than in the negative group in endometrial carcinoma. The distinct concordance was observed between aromatase and VEGF (P<0.01).Conclusions Aromatase and COX-2 were over expression in endometrial carcinoma and there was a high coincidence between them. These results indicated that aromatase and COX-2 maybe exert synergistic action in the carcinoma development. Probably there was a right feedback modulation mechanism between them. It is important to detect aromatase and COX-2 together in order to survey the development of endometrial carcinoma.Aromatase and VEGF were over expression in endometrial carcinoma and there was a coincidence between them. These results indicate that estrogen by upregulating VEGF and inducing newly formed blood vessels could be one of aromatasemodulating endometrial carcinogenesis mechanism.