Expressions And Significance Of Bcl-2/Bax, Fas/Fasl And Caspase3 In Women With Endometrial Polyps

Background and ObjectiveEndometrial polyps(EMPs)is a common gynecologic disease,resulting in abnormal uterine bleeding(AUB).It can occur at any age after the menarche,most common at 50years old.The prevalence of EMPs in the general female women is estimated to be 25%approximately.Although the incidence rate of EMPs has been increasing with the spread use of transvagianalsonograph,sonohysterography and hysterscopy,the pathogenesis of EMPs is poorly understood.Traditionally,it can be considered as a kind of chronic inflammation,however,recent evidence has suggested that the dysregulated apoptosis may play a role in the pathogenesis of EMP.Apoptosis,a programmed cell death,palys an important role in development and maintenance of tissue homeostasis.Apoptosis is a kind of autonomic cell death that is widely existed in many physiological and pathological conditions.Many kinds of apoptosis related genes and its products can regulate precisely apoptosis at the molecular level.Cells undergo apoptosis through two major pathways.One depends on the participation of mitochondria.Proapoptotic and antiapoptotic members of the Bcl-2 family regulate the mitochondrial pathway,such as Bcl-2 and Bax.The ratio of Bax to Bcl-2 regulates apoptosis.The second pathway involves the interaction of a death receptor,such as Fas receptor with its ligand Fasl. Caspases(cysteine-containing aspartate-specific proteases)family play a central role in regulation and execution of cell apoptosis.The extrinsic and intrinsic pathways for Caspase activation converge on downstream effector Caspases,which ultimately results in apoptotic cell death.Uterine endometrium has a regular change during the menstrual cycle. Apoptosis and its related genes have an important role in the regulating of this physiological progress,but the role of apoptosis mechanism playing in the pathogenesis of EMPs remains unclear.The objective of the present study is to investigate the expressions of Bcl-2/Bax,Fas/Fasl and Caspase3 in endometrial polyps,and to evaluate the possible roles playing in the pathogenisis of EMPs.Materials and MethodsEndometrial biopsies were obtained from 55 women with uterine leiomyoma undergoing hysterectomy and from 63 women with EMPs undergoing polypectomy under hyteroscopy during Janunary 2004 to March 2006 at the Women's Hospital, School of Medicine,Zhejiang University.Expressions of Bcl-2/Bax,Fas/Fasl and Caspase3 were detected using immunohistochemistry method(EnVision system)in the control endometirum and the EMPs.Results1.Bcl-2 and Bax was mainly immunostained in the glandular epithelial cells of the control endometrium and the EMPs.Bcl-2 expression in the EMPs of the proliferative and secretory phase were all significantly higher than that in the control endometrium(P＜0.05).Bax expression in the proliferative phase had no significant difference between two groups (P＞0.05),however,Bax expression in the EMPs of the secretory phrase was significantly lower than that in the control endometrium(P＜0.05).2.Fas and Fasl was also mainly immunostained in the glandular epithelial cells of the control endometrium and the EMPs.Fas expression in the EMPs of the proliferative phase and the secretory phase were all significantly lower than that in the control endometrium(P＜0.05).There was no significant difference of Fasl expression in the proliferative phase between two groups(P＞0.05),however,Fasl expression in the EMPs of the secretory phase was significantly lower than that in the control endometrium(P＜0.05).In addition,Fasl expression of the EMPs and the control endometrium were statistically higher in the secretory phase than that in the proliferative phase.3.Caspase3 was chiefly immunostained in the glandular epithelial cells of the control endometrium and the EMPs.In the proliferative phase Caspase3 expression had no difference between two groups(P＞0.05).In the EMP Caspase3 expression in the secretory phase was significantly higher than that in the prolifrative phase(P＜0.05),but lower than that in the normal endometrium(P＜0.05).4.In the EMP there was no significant correlation between Bcl-2 expression and Fas expression(r=-0.083,P=0.174).But in the control endometrium Bcl-2 expression had a negative correlation with Fas expression(r=-0.934, p＜0.01).Conclusion1.The expression of Bcl-2/Bax and Fas/Fasl was correlated with the cyclic changes in the control endometrium.Bcl-2/Bax was in the proliferative phase whereas Fas/Fasl,in the secretory phase.2.Bcl-2 expression upregulated in the proliferative phase and Bax expression downregulated in the secretory phase leaded to the elevated ratio of Bcl-2 to Bax,resulting in the failure of the normal cyclical apoptosis in the EMPs during the late secretory phase.3.The expressions of the Fas and Fasl in the normal endometrium of the proliferative phase and the secretory phase were all significantly higher than those in EMPs,suggesting a role of Fas/Fasl playing in the pathogenesis of EMPs.4.Caspase3 expression in the EMPs of the secretory phase was elevated although the expression was significantly lower than that in the normal endometrium,indicating a role of Caspase3 playing in the pathogenesis of EMPs.5.The association of Bcl-2 expression with Fas in the EMP suggests that the dysregulated expression of Bcl-2,Fas with its associated ligand may contribute to the pathogenesis of EMPs.