Expression and function of cyclooxygenase-2 in endometrial carcinoma

目的:了解子宫内膜癌中环氧化酶-2(cyclooxygenase-2,COX-2)在mRNA与蛋白水平的表达及其临床意义,探讨其与血管生成、细胞凋亡及激素受体的关系.方法:收集41例正常子宫内膜组织及52例子宫内膜癌组织,总结相关的临床资料.采用RT-PCR的方法研究COX-2 mRNA水平的表达.用免疫组织化学方法研究COX-2、血管内皮生长因子(vascular endothelial growth factor,VEGF)、B-cell lymphoma protein 2(Bel-2)蛋白水平表达,并用CD105为标记计数微血管密度(microvansicular density,MVD),用TUNEL方法计数凋亡细胞数.结果:(1)COX-2 mRNA在内膜癌中的表达较正常子宫内膜增强(P＜0.001).(2)COX-2蛋白在内膜癌中的表达较正常内膜增强(P＜0.001).(3)COX-2蛋白表达在高、中分化子宫内膜癌组较低分化组升高(P:0.020),与手术分期、病理类型、肌层浸润深度及淋巴结转移无相关性.COX-2 mRNA水平与以上各项因素均无相关性.(4)COX-2的mRNA表达水平与蛋白表达水平无相关性(P=0.125,r=0.222).(5)COX-2蛋白表达的升高伴有VEGF、MVD和Bcl-2的升高及凋亡细胞减少(P均＜0.05).(6)COX-2的表达增强与ER-α和ER-β蛋白表达无相关性,但与孕激素亚型A和B(PRA、PRB)的表达升高有相关性,P值分别为0.031和0.007.结论:(1)子宫内膜癌中COX-2在mRNA水平及蛋白水平均较正常子宫内膜中明显升高.(2)COX-2的蛋白高表达与肿瘤较好分化相关,而与病理类型、手术分期、肌层浸润深度及淋巴结转移均无相关性.mRNA与以上各因素均无相关性.(3)子宫内膜癌中COX-2的表达增强伴有VEGF蛋白水平升高及微血管密度增加.(4)子宫内膜癌中COX-2的表达增强伴有Bcl-2蛋白水平升高及肿瘤细胞凋亡受到抑制.(5)在内膜癌COX-2阴性与阳性两组间,雌激素受体表达差异无统计学意义,而PRA及PRB在阳性组的表达均较阴性组升高.Objective: To evaluate the cyclooxygenase-2 ( COX-2) expression at mRNA and protein levels , as well as its clinical significance, and to study the correlation of COX-2 with angiogenesis, apoptosis and estrogen or progestron receptors. Methods: Forty-one samples of normal endoraetrium tissues and 52 ones of endometrial carcinomas( EC) were collected,together with their corresponding clinical information. RT-PCR was adopted to determine the expression of COX-2 mRNA. Immunohistochemical staining was engaged to evaluate the protein expression of COX-2, VEGF, Bcl-2 and the MVD marked by CD105. And TUNEL was used to count the apoptosis cells. Results: (1) Significantly higher mRNA and protein levels of COX-2 were found in endometrial carcinomas than in normal endometrial tissues ( P＜0.001) . (2) At protein level ,COX-2 expression was related to the grade(P =0.020) , but had nothing to do with the stage, pathological type, depth of myometrium invasion and lymph node metastasis. Neither did the level of COX-2 mRNA with all the factors above. (3)The level of COX-2 mRAN had nothing to do with that of protein(P =0. 125, r =0. 222). (4) The higher the expression of COX-2 protein was, the higher that of VEGF,MVD or Bcl-2 was,and the lower the count of apoptosis cells was P＜0.05. (6)The upregulation of COX-2 protein had no correlation with ER-α and ER-β . But it had positive correlation with PRA and PRB,P was 0.031 and 0.007 .respectively. Conclusion: (1)The expression of COX-2 is significantly higher in EC than in normal endometrium tissue, not only at the mRNA level, but also at protein level. ( 2 ) At protein level, COX-2 expression is related to the grade, but has nothing to do with the stage, pathological type, depth of myometrium invasion and lymph node metastasis. Neither does the level of COX-2 mRNA with all the factors above. (3)The upregulation of COX-2 protein in EC correlates with the increase of VEGF protein and MVD. (4) The upregulation of COX-2 protein in EC correlates with the increase of Bcl-2 protein and the decrease of apoptosis cells. (5)The upregulation of COX-2 protein in EC has no significant correlation with ER expression, but has something to do with the increase of PRA and PRB.国家自然科学基金; 教育部科学技术研究重大项目中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)06657-6634