Correlative Studies Of NF-κB,ICAM-1 And VEGF In Endometriosis

BackgroundEndometriosis, the common gynecology disease, occupying 30% of gynecological operations, is a chronic recurrent disease affecting 10% of the female population causing infertility, dysmenorrhea, dyspareunia and pelvic pain. Although the diagnosis of endometriosis may be suggested by the history and physical examination, its final diagnosis can only be acquired through laparoscopy or laprotomy. There are still no effective and specific chemical markers. Suppression of ovarian activity by hormonal therapy or operation, as the main therapeutic interventions today, can relieve symptoms and improve pregnant rate to some extend, but always with severe adverse effects and high relapse rate. No exact pathophysiology of this enigmatic disease is the principal reason that restrict its clinical and basic study. Hence, investigating its pathogenesis has been becoming a ugent task of gynaecologist and other medical scientist. Recently, some study revealed that the implantation growth and metastasis of ectopic endometrium resembling malignant tumor's biological behaviors plays a major role in the development and maintenance of endometriosis. Nuclear factor-kappaB (NF-kB), a key nuclear transcription factor actived by mitogen, plays an important role in accommodation of cytokine, adherence factor and vassular active factors in the processes of formation growth management and prognosis in many malignant tumor. Intercellular adhesion molecule-1 (ICAM — 1) and vascul arendothelia growthfactor (VEGF) , obtained more and more reconstruction in recent studies of endometriosis, are the most important stimulating factor in pathogenesis of malignancy .Some studies showed that ICAM— 1 and VEGF are the downstream and controlled gene of NF-kB, but their role in the pathogenesis of endometriosis are not clear yet.Section oneRoles of NF-kB ICAM—1 and VEGF in pathogenesis of endometriosisObjectives: To detect the expression of NF-kB ICAM—1 and VEGF in ectopic endometrium eutopic endometrium and normal endometrium (control group), investingate the relationships of NF-kB ICAM— 1 and VEGF with endometriosis, and explore the possible roles of these factors in etiopathogenesis of endometriosis.Methods : Immunohistochemistry was used to examine the NF-kB ICAM— 1 and VEGF protein expression in 35 cases with normal endometrium, 48 eutopic endometrium of endometriosis and 76 ectopic endometrium. The results were analyzed with SPSS 10.0 statistical software.Results (1)The immunoreactivity of NF-kB ICAM—1 and VEGF was found predominantly in the cytoplasm of glandular epithelial cells in ectopic and eutopic endometrium of endometriosis and partly found in stroma cell or vascular endothelial cell in eutopic ednometrium. It was significant to express differently in three groups , with the level of expression in ectopic endometriotic tissues the highest ,and in the normal endometrium the lowest( P<0.001); ?The expression levels of NF-kB>ICAM — 1 and VEGF value changed with the normal menstrual cycle of three kinds endometrium. The expression levels of NF-kB and VEGF in secretory phase endometrium were significantly higher than that in the proliferative phase endometrium (P<0.05); (3)NF-kB and ICAM-lwere positively relative among the expression levels of normal endometrium -, eutopic and ectopic endometrium, with the coefficient correlation 0.688, 0.773 and 0.777 respectively(P<0.01); NF-kB and VEGF was positively relative among the expression levels of normal endometrium , eutopic and ectopic endometrium, and the coefficient correlation was 0.660n 0.733 and 0.820 respectively(P<0.01).Conclusions: ?It suggested that abnormal expression of NF-kB ^ ICAM—1and VEGF in ectopic endometrium maybe correlate with etiopathogenesis of endometriosis; (2)NF-kB ; acting as a key nuclear transcription factor; played an "penstock" role in the accommodation of ICAM-1 and VEGF in the developing process of endometriosis; (3)NF-kB ^ ICAM — 1 and VEGF play roles in the formation of menstrual cycle > nidation of spermatovum and development of embryo possiblely. ?There were great possibilities that innate differences of eutopic endometrium acted as the key factor in etiopathogenesis of endometriosis. The hypothesis of "eutopic endometrium determinism" will provide a new explanation for the etiopathogenesis and a new target for the management of endometriosis.Section twoClinical significance of NF-kB .. ICAM—1 and VEGF expression in eutopicendometrium of endometriosisObjective: To elucidate the relationship between the expression of NF-kB -. ICAM—1 and VEGF in eutopic endometrium with clinical stage> chronic pelvic cavity pain > infertility and recurrence of endometriosis.Methods: Histological sections of eutopic endometrium in 83 patients with endometriosis were detected by immunohistochemistry and analyzed with patients follow- up material; and the results were analyzed with SPSS 10.0 statistical software.Results: ?There were statistically differences regarding expression level of NF-kB and ICAM—1 in euptice endometrium between patients with or without chronic pelvic cavity pain(p<0.05); but foregoing difference was no significance in the expression level of VEGF (p>0.05); (2) It was significantly different in expression level of VEGF among stage I ~IV(p<0.05); and the expression level of VEGF in stage I ~ II was significantly higher than that in stageIII~IV; but these differences were no significance in comparision with expression level of NF-kB and ICAM—1 among stage I ~IV(p>0.05); ?There were statistically differences in expression level of NF-kB^ ICAM—1 and VEGF in euptice endometrium between pregnant and infertilie patients after the operation of remaining potentia generandi(P<0.05); ?The patients with high level of NF-kB . ICAM-1 and VEGF expression were with poor prognosis as to the patients with low level of NF-kB and VEGF expression(P<0.05); because the former patient was more easier recidivation than the latter.Conclusion: (T)It suggested that abnormal expression of NF-kB -> ICAM~ 1 and VEGF in eutopic endometrium maybe correlate with etiopathogenesis of chronic pelvic cavity pain in endometriosis; ?It was possible that abnormal expression of NF-kB n ICAM — 1 and VEGF in eutopic endometrium maybe correlate with etiopathogenesis of infertility in endometriosis; (3)The staging of revisied American fertility society with endometriosis is circumscribed. If the metered data about pain and infertility could be included in the staging index; its clinical application will be more significant. (4)It was feasible that expression of NF-kB ; ICAM— 1 and VEGF in eutopic endometrium could act as the prognostic index.