【作者】 向萍；

【导师】 张怡；

【作者基本信息】 中南大学 ， 临床医学， 2013， 博士

【摘要】 目的：通过观察Cripto-1、β-catenin蛋白在卵巢子宫内膜异位囊肿、子宫腺肌病、卵巢子宫内膜异位囊肿合并子宫腺肌病的异位、在位内膜是否存在表达差异性及相关性,探析二者在异位病灶形成过程中的作用及意义。方法：应用免疫组化SP二步法检测Cripto-1、β-catenin蛋白在卵巢子宫内膜异位囊肿(巧囊组)、子宫腺肌病(腺肌病组)、卵巢子宫内膜异位囊肿合并子宫腺肌病(巧囊合并腺肌病组)异位、在位内膜的表达特点,并与正常子宫内膜(对照组)进行比较。结果：1.Cripto-1蛋白在巧囊组、腺肌病组及巧囊合并腺肌病组异位、在位内膜中的阳性表达率两两比较均无显著性差异(P>0.05),均显著高于对照组的阳性表达率(P<0.05)。巧囊组异位内膜、腺肌病组异位内膜、巧囊合并腺肌病组巧囊异位内膜及腺肌病异位内膜的阳性表达率分别为46.67%、53.33%、57.78%及66.67%,两两比较无显著性差异(P>0.05),以上三组的在位内膜中的阳性表达率分别为62.22%、64.44%及75.56%,两两比较亦无显著性差异(P>0.05),均显著高于对照组的阳性表达率17.78%(P<0.05)。巧囊组异位内膜中Ⅲ～Ⅳ期的阳性表达率58.06%显著高于Ⅰ～Ⅱ期的阳性表达率21.43%(P<0.05)；在巧囊合并腺肌病组巧囊异位内膜中Ⅲ～Ⅳ期的阳性表达率66.67%显著高于Ⅰ～Ⅱ期的阳性表达率33.33%(P<0.05)。2.β-catenin蛋白在巧囊组、腺肌病的异位内膜及在位内膜的阳性表达率两两比较有显著性差异(P<0.05),均显著低于对照组的阳性表达率86.67%(P<0.05)。巧囊合并腺肌病组中巧囊异位内膜、腺肌病异位内膜的阳性表达率与在位内膜相比均有显著性差异(P<0.05),均显著低于对照组(P<0.05)。巧囊组异位内膜、腺肌病组异位内膜、巧囊合并腺肌病组巧囊异位内膜及腺肌病异位内膜中的阳性表达率分别为31.11%、24.44%、26.67%及17.78%,两两比较无显著性差异(P>0.05)。在巧囊组、腺肌病组及巧囊合并腺肌病组的在位内膜的阳性表达率分别为62.22%、57.78%及66.67%,两两比较无显著性差异(P>0.05),均显著低于对照组(P<0.05)。巧囊组异位内膜中Ⅲ～Ⅳ期的阳性表达率19.35%显著低于Ⅰ～Ⅱ期的阳性表达率57.14%(P<0.05)；巧囊合并腺肌病组巧囊异位内膜中Ⅲ～Ⅳ期的的阳性表达率15.15%显著低于Ⅰ～Ⅱ期的阳性表达率58.33%(P<0.05)。在巧囊组、腺肌病组的异位内膜、在位内膜及对照组正常子宫内膜中胞浆阳性率两两比较有显著性差异(P<0.05)。在巧囊合并腺肌病组巧囊异位内膜、腺肌病异位内膜中胞浆阳性率显著高于在位内膜的胞浆阳性率(P<0.05),以上三组胞浆阳性率均显著高于对照组(P<0.05)。3. Spearman等级相关分析显示Cripto-1与β-catenin蛋白在子宫内膜异位性疾病中的在位内膜、异位内膜中表达存在负相关,差异有统计学意义(P<0.05),在对照组中无明显相关性(P>0.05)。结论：1.Cripto-1蛋白在卵巢子宫内膜异位囊肿及子宫腺肌病的异位内膜、在位内膜的表达明显高于正常子宫内膜,β-catenin蛋白则明显低于正常子宫内膜,提示二者与子宫内膜异位性疾病的发病有关。2.Cripto-1与β-catenin蛋白在三组的在位内膜既已发生改变,靶点均位于在位内膜,提示与在位内膜的迁徙侵袭及异位定植相关。3.Cripto-1、β-catenin蛋白随内异症临床分期存在差异性表达,可望作为评估内异症病情严重程度及病情进展的指标。4.Cripto-1与β-catenin蛋白在子宫内膜异位性疾病中的在位内膜、异位内膜中呈负相关,提示二者可能共同参与异位病灶形成。更多还原

【Abstract】 Objective:To investigate the expression and relationship between Cripto-1and (3-catenin in paired ectopic and eutopic endometrium of ovarian endometriomas, adenomyosis and ovarian endometriomas concomitant with adenomyosis patients, so as to explore their roles in the pathogenesis of ectopic focus progression.Methods:To detect the expression profile of Cripto-1and β-catenin protein in paired ectopic and eutopic endometrium of45patients with ovarian endometriomas (Chocolate cyst group),45patients with adenomyosis (Adenomyosis group),45patients with ovarian endometriomas concomitant with adenomyosis (Chocolate cyst combined with adenomyosis group) and45cases of normal endometrium (control group) by Immunohistochemistry.Results:1.The positive ratio of Cripto-1protein expression was no significantly differences in ectopic and eutopic endometrium of Chocolate cyst group、Adenomyosis group and Chocolate cyst combined with adenomyosis group (P>0.05), and up-regulated significantly in comparison of control group (P<0.05). The positive ratio of Cripto-1protein was46.67%for ectopic endometrium of Chocolate cyst group,53.33%for ectopic endometrium of Adenomyosis group,57.78%for ectopic endometrium of chocolate cyst in Chocolate cyst combined with adenomyosis group and66.67%for ectopic endometrium of adenomyosis in Chocolate cyst combined with adenomyosis group, which is similar between the two groups (P>0.05). The positive ratios of the above three groups were62.22%、64.44%and75.56%, which is no significantly difference between groups (P>0.05) and significantly higher than the positive ratio of control group (P<0.05). The positive ratio of stage III-IV in ectopic endometrium of Chocolate cyst group were higher than that of stage Ⅰ～Ⅱ with significance (P<0.05). Meanwhile the positive ratio of stage III-IV in ectopic endometrium of chocolate cyst of Chocolate cyst combined with adenomyosis group were significantly higher than that of stage Ⅰ～Ⅱ (P<0.05).2.The positive ratio of β-catenin protein expression was significantly different in paired ectopic and eutopic endometrium between Chocolate cyst group and Adenomyosis group (P<0.05), and down-regulated significantly in comparison of that of control group (86.67%). The positive ratio of β-catenin protein expression in ectopic endometrium of chocolate cyst and ectopic endometrium of adenomyosis in Chocolate cyst combined with adenomyosis group was significantly different versus paired eutopic endometrium (P<0.05), and decreased significantly in comparison of control group (P<0.05). The positive ratio of β-catenin protein was31.11%for ectopic endometrium of Chocolate cyst group,53.33%24.44%for ectopic endometrium of Adenomyosis group,26.67%for ectopic endometrium of chocolate cyst of Chocolate cyst combined with adenomyosis group and17.78%for ectopic endometrium of adenomyosis of Chocolate cyst combined with adenomyosis group, which is no significantly differences between groups (P>0.05). The positive ratios of the above three groups were62.22%、57.78%and66.67%, which is also no significantly differences between groups (P>0.05)and significantly lower than the positive ratio of control group (P<0.05). The positive ratio of stage III-IV in ectopic endometrium of Chocolate cyst group were lower than that of stage Ⅰ～Ⅱ with significance (P<0.05). Meanwhile the positive ratio of stage Ⅲ～Ⅳ in ectopic endometrium of chocolate cyst of Chocolate cyst combined with adenomyosis group were lower than that of stage Ⅰ～Ⅱ with significance (P <0.05).The cytoplasm positive ratio of P-catenin protein expression was significantly different between the paried ectopic and eutopic endometrium among the Chocolate cyst group, Adenomyosis group and Chocolate cyst combined with adenomyosis group, comparing with that of control group (P<0.05).3.The Spearman analysis showed that negative correlations between Cripto-1protein and β-catenin protein in paired ectopic and eutopic endometrium of the Chocolate cyst group, Adenomyosis group and Chocolate cyst combined with adenomyosis group(P<0.05).Conclusion:1.The expression of Cripto-1protein was significantly up-regulated in eutopic endometrium of endometriosis and adenomyosis versus the normal endometrium while β-catenin protein was significantly down-regulated, which indicated that they might be involved in the pathogenesis of endometriosis and adenomyosis.2.The target site of Cripto-1protein and β-catenin protein was the eutopic endometrium, which suggested that the two proteins were related with the mechanism of migration, invasion and plantation of eutopic endometrial cells.3.The expression of Cripto-1protein and β-catenin protein were relevant with different clinical stages of endometriosis, which indicated that they might be a promising indicator of assessing the disease severity and progression.4.There was a negative relationship between the Cripto-1protein and β-catenin protein in paired ectopic and eutopic endometrium of endometriosis and adenomyosis, which suggested that they may involved in the development of ectopic focus progression.更多还原