Expression Of COX-2,VEGF And MVD In The Endometrium Of Patients With Sympotomatic Uterine Leiomyomas

Objective: The control of normal menstruation rely on normal function of blood vessel and coagulation, while the function of blood vessel rely on the quality and quantity of the vessel in the course of reconstruction of the endometrium. Vascular endothelial growth factor(VEGF)is the main factor of regulating vascular growth in physiological and pathological situation. VEGF is ascribed with a variety of biological effects including increasing the permeability of capillaries, stimulating mitogenesis and proliferation of endothelial cells and then inducing angiogenesis. Cyclooxygenase is one of the rate-limiting enzymes in the synthesis of PGs in metabolism of arachidonic acid. COX-2 ,as one of the theisoforms, together with VEGF are the angiogenisis activators which have been paid more attention to in recent years. As the main factor of regulating vascular growth, COX-2 and VEGF play an important role in controling the quality and quantity of vascular in the course of reconstrction of the endometrium.Microvessel density(MVD)is regarded as the ideal index in judging the quantity of the blood vessel.This experiment is aimed at exploring the changes of endometrial microenvironment in patients with uterine leiomyomas and to seek a kind of conservative treatment theoretically for patients with sympotomatic uterine leiomyomas by investigating the expressions of VEGF,COX-2 and MVD in endometrium of patients with uterine leiomyomas.Methods: 53 patients with uterine leiomyomas according to pathological examination were divided into two groups (groupA and group B) based on the symptom of menorrhagia and healthy women with normal menstruation were recruited into group C as healthy controls.Each group were divided into different subgroups according to pathological examination of the endometrium.33 patients with sympotomatic uterine leiomyomas in group A consisted of 13 patients with proliferative phase endometrium, 11 patients with secretory phase endometrium, 6 patients with simple hyperplasia and 3 patients with complex hyperplasia. 20 patients with asympotomatic uterine leiomyomas were recruited into group B with 15 with proliferative phase and 11 with secretory phase. 12 healthy women of group C as healthy controls were consist of 6 with the proliferative phase and 6 with the secretory phase. Immunohistochemistry was used to investigate the expression of COX-2,VEGF,MVD in the endometrium of the three groups. Result-judging criterion was that pale brown dyeing in cellular serosa or nuclei was defined as positive reaction. Immunoreactivity was measured with a computerized image analysis system in a quantitative manner. Acquired data were analysed by SPSS 12.0 statistical software. The date of COX-2,VEGF and MVD in each group were described by x|-±s and compared by One-Way ANOVA. Correlations of COX-2, VEGF and MVD were analysed by Pearson correlation.It is considered to be significant at a probability value of less than 0.05.Results: The expression of COX-2 and VEGF protein in endometrium of each group: COX-2 and VEGF protein were expressed in three groups,which were expressed predominnatly in the glandular epithelial cell serosa and weakly in stromal cells.There were some expression in vascular endothelial cells.The expression of COX-2 protein and VEGF protein in endometrium of proliefrative and secretory phase in group A was higher than that in group B and C (P<0.05). The expression in endometrium of simple hyperplasia and complex hyperplasia phase was significantly lower than that of the proliefrative phase in each group (P<0.001).There were no significnatly dieffrence in the expression of COX-2 and VEGF between group B and C in the endometrium of proliefrative phase or secretory phase (P>0.05). There were no significnatly dieffrence in the expression of COX-2 and VEGF in the three groups with the endometrium of proliefrative phase or secretory phase (P>0.05).The expression of MVD in endometrium of each group: The positive expression of CD34-marked MVD in endometrium of proliefrative and secretory phase in group A was significantly higher than that of group B and C (P<0.05). The expression in endometrium of simple hyperplasia and complex hyperplasia phase were similar but significantly lower than that of the proliefrative phase in each group (P<0.001). There were no significnatly difference in the expression of MVD between group B and C in the endometrium of proliefrative phase or secretory phase (P>0.05). There were no significnatly dieffrence in the three groups with the endometrium of proliefrative phase or secretory phase (P>0.05).Correlations of VEGF,COX-2 and MVD expressions in group A: In all the subgroups, the expression of COX-2 was positively correlated with that of VEGF (r=0.779,P<0.05;r=0.626 , P<0.05,r=0.666 , P<0.01). The expression of MVD was positively correlated with COX-2 and VEGF (r=0.829,P<0.05;r=0.798,P<0.05).Conclusion: There were increasing expression of COX-2,VEGF and MVD in the endometrium of patients with sympotomatic uterine leiomyomas ,especially in hyperplasia endometrium, but no changes in the endometrium of patients with asympotomatic uterine leiomyomas. Abnormal changes of endomertrial microenvironment is responsible for menorrhagia of patients with uterine leiomyomas.This conclusion provided a reliable theoretical proof of conservative treatment of patients with sympotomatic uterine leiomyomas.