Expression Of Survivin And Bcl-2 In Endometriosis And Their Significance

[Objective] To detect the expression of anti-apoptosis Survivin and Bcl-2 in endometriosis and normal endometrium, analyze their correlation in ectopic endometrium and eutopic endometrium, try to explore the role of apoptosis in the pathogenesis of endometriosis.[Methods] Paraffin blocks of endometriotic tissue from 40 cases with complete clinical date were collected by random choosing from date of deparetment of gynaecology and obstetrics of ChangZheng hodpital and JinShan hospital of FUDAN university, from January 2006 to Novermber 2007.A11 patients had laparoscopy or laparotomy and comfirmed by pathological examination. The stage of the disease was performed according to the revised American Fertility Society classification. There were zero patient with stageⅠdisease, 12 with stageⅡ, 18 with stageⅢ, and 10 with stageⅣ. The menstrual cycle was divided into two phases according to the histopathologic evaluation: proliferative(n=21) and secretory(n=19). Of 40 casess of endometriosis,28 cases of eutopic endometrium (13 proliferative;15 secre- tory) were collected.The mean age of patients was (39.50±6.57) years (range 28-52 years). Thirty blocks of normal endometrium (14 proliferative; 16 secretory) from hysterectomy specimens performed non-endometrial pathology, such as leiomyoma were included as controls. The mean age of patients was (43.25±5.88) years (range 32-55 years). Patients with an irregular menstrual cycle and those who received hormonal therapy or have medical disease at the time were not included in this study. All the specimens were fixed with formalin and embedded routinely with paraffin, the thickness for every section was 4μm.The expression of Survivin and Bcl-2 in all the specimens were detected by EnVision method of immunohistochemistry. Apoptosis index in eight blocks of normal endometrium (4 proliferative; 4 secretory), eight blocks of ectopic endometrium (4 proliferative;4 secretory) and six blocks of eutopic endometrium (3 proliferative;3 secretory) was detected by TUNEL. SPSS14. 0 was used to analyze the data, the Spearman rank correlation coefficient was also used to analyze the relation between Survivin and Bcl-2 gene expression levels in endometriotic tissues. A level of P less than 0.05 was accepted as statistically significant.[Result]1 .Apoptosis index change in endometriosis and normal endometrium: Apoptosis index in normal proliferative stage and normal secretory stage endometrium was (33.25±6.99)% and (69.50±10.85)% respectively, there was obvious statistical significance (P<0.01) . Apoptosis index in eutopic proliferative stage and eutopic secretory stage endometrium was (19.00±1.00)% and (25.00±3.00)% respectively, there was statistical significance (P<0.05). Apoptosis index in ectopic proliferative stage and ectopic secretory stage endometrium was (4.00±0.82)% and( 6.25±1.70)% respectively, there was no statistical significance (P>0.05) . Apoptosis index in normal endometrium ,eutopic endometrium and ectopic endometrium was (5.13±1.73)%,(22.00±3.85)% and (51.37±21.14)% respectively, there was statistical significance (P<0.05) .2. The expression of Survivin in endometriosis and normal endometrium: The expression of Survivin was negative in 14 cases of normal proliferative stage endometrium, the positive expression rate of Survivin was 6.25% in 16 cases of normal secretory stage endometrium, but there was no statistical significance for the Survivin expression rate in these two phases of normal endometrium (P>0.05) . In endometriosis, the expression of Survivin immunereaction were found predominately in the glandular epithelial cells. The positive expression rate of Survivin was 75.00% in 40 cases of ectopic endometrium,and in proliferative stage and secretory stage the positive expression rate of Survivin was 76.19% and 73.68% respectively, but there was no statistical significance in these two phases of endometriosis (P>0.05). The positive expression rate of Survivin in 28 cases of eutopic endometrium with endometriosis was 50.00% ,and in proliferative stage and secretory stage the positive expression rate of Survivin was 46.15% and 53.33% respectively, but there was no statistical significance in these two phases of eutopic endometrium(P>0.05) .There was obvious statistical significance in these there roups (normal endometrium 3.33%;eutopic endometrium 50.00%;ectopic endometrium 75.00%, P<0.01) ,that is to say the positive expression rate of Survivin in ectopic endometrium and in eutopic endometrium was obviously higher than that in normal endometrium(P<0.017), but at the level of 0.017 there was no statistical significance between ectopic endometrium and eutopic endometrium(P>0. 017).3. The expression of Bcl-2 in endometriosis and normal endometrium: There was expression of different degree in normal endometrium. The expression of Bcl-2 immunereaction were found predominately in the glandular epithelial cells,and in stroma cells, helicine artery, smooth muscle cells can been found weak enpression.The positive expression of Bcl-2 in proliferative phase and secretory phase of normal endometrium was 42.85% and 6.25% respectively, there was statistical significance for the Bcl-2 expression rate in these two phases of normal endometrium(P<0.05). In endometriosis, the expression of Bcl-2 immunereaction was also found predominately in the glandular epithelial cells. The positive expression rate of Bcl-2 was 80.00% in 40 cases of ectopic endometrium,and in proliferative stage and secretory stage the positive expression rate of Bcl-2 was 85.71% and 73.68% respectively, but there was no statistical significance in these two phases of endometriosis (P>0.05) . The positive expression rate of Bcl-2 in 28 cases of eutopic endometrium with endometriosis was 57.14% ,and in proliferative stage and secretory stage the positive expression rate of Bcl-2 was 76.92% and 40.00% respectively, there was statistical significance in these two phases of eutopic endometrium (P>0.05) .There was obvious statistical significance in these there roups (normal endometrium 23.33%;eutopic endometrium 57.14%;ectopic endometrium 80.00%,P<0.01) ,that is to say the positive expression rate of Bcl-2 in ectopic endometrium and in eutopic endometrium was obviously higher than that in normal endometrium(P<0.017), but at the level of 0.017 there was no statistical significance between ectopic endometrium and eutopic endometrium(P>0.017).3. The expression of Survivin and Bcl-2 in ectopic endometrium and eutopic endometrium is positive correlation.[Conclusion]1. Apoptosis index was lower and lower in normal endometrium without endometriosis, eutopic endometrium with endometriosis, ectopic endometrium with endometriosis. Apoptosis index showed obvious cyclic change in eutopic endometrium with endometriosis and normal endometrium without endometriosis. This result indicate that apoptosis index was low in ectopic and eutopic endometrium, favor abnormal proliferative, destroy the balance between proliferative and apoptosis, so it may contribute to the formation and progression of endometriosis.2. No Survivin expression showed in proliferative phase of normal endometrium, and weak expression in secretory phase of normal endometrium .The Survivin expression was low in eutopic endometrium and in ectopic endometrium the positive expression was much higher than that in normal endometrial cells. Survivin was not correlated with the phase of menstrual cycl in normal endometrium, eutopic endometrium and ectopic endometrium. This result indicate that Survivin can inhibit cell apoptosis in ectopic endometrium, destroy the balance between proliferative and apoptosis, favor abnormal proliferative, so it may contribute to the formation and progression of endometriosis.3. The expression of Bcl-2 was higher and higher in normal endometrium without endometriosis, eutopic endometrium with endometriosis, ectopic endometrium with endometriosis. The expression of Bcl-2 showed obvious cyclic change in eutopic endometrium with endometriosis and normal endometrium without endometriosis in that Bcl-2 was higher in proliferative phase than that in secretory phase and had no cyclic change in ectopic endometrium. This result demonstratred that the means which Bcl-2 inhibit apoptosis was not correspond with Survivin, but up-regulation of Bcl-2 may cooperatively contribute to survival and invasion of endometriosis.4. The expression of Survivin and Bcl-2 in ectopic endometriun and eutopic endometrium with endometriosis was positive correlation with each other, this implyed these two genes may cooperatively take part in the formation and progression of endometriosis.