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COX-2在子宫内膜腺癌组织中的表达及其与Ki-67、Caspase-3、CD34和E-cadherin的关系
Expression of Cyclooxygenase-2 in Human Endometrial Adenocarcinoma: Correlation with Ki-67, Caspase-3, CD34 and E-cadherin
【作者】 牛兆山;
【导师】 纪祥瑞;
【作者基本信息】 青岛大学 , 病理与病理生理学, 2008, 硕士
【摘要】 目的:探讨环氧合酶-2(Cyclooxygenase-2,COX-2)、Ki-67、门冬氨酸特异的胱氨酸蛋白酶-3(Cysteinyl aspartate-specific proteinase-3,Caspase-3)、CD34、上皮型钙粘附蛋白(E-cad,E-cadherin)在子宫内膜腺癌中的表达与临床病理参数间的关系,进而阐明它们在于宫内膜腺癌发生发展中的作用及它们之间可能存在的关系。方法:应用免疫组化Envision法检测20例正常子宫内膜和70例子宫内膜腺癌中COX-2、Ki-67、Caspase-3、CD34和E-cadherin表达情况。结果:子宫内膜腺癌组织中COX-2、Ki-67蛋白表达阳性率及MVD均明显高于正常子宫内膜组织(Hc=22.17、27.81,P=0.0000,t=12.67,P<0.001),而Caspase-3及E-cadherin表达阳性率则明显低于正常子宫内膜组织(Uc=5.097,X~2=18.79,P<0.001);COX-2表达与病人年龄、病理分级及手术-病理分期均无关(Hc=1.050、5.566、5.358,P>0.05),而与子宫肌层浸润深度及淋巴结转移有关(Uc=3.015、5.237,P<0.05、0.01);Ki-67与病人年龄及手术-病理分期无关(Hc=3.590、5.880,P>0.05),而与病理分级、子宫肌层浸润深度及淋巴结转移有关(Hc=8.504,Uc=2.5 14、2.963,P<0.05、0.01);Caspase-3与病人年龄、手术-病理分期、子宫肌层浸润深度及淋巴结转移均无关(UC=1.273,Hc=4.371,Uc=1.374、1.077,P>0.05),而与病理分级有关(Hc=7.320,P<0.05);MVD与病人年龄、病理分级无关(t=-1.673,F=2.09,P>0.05),而与手术-病理分期、子宫肌层浸润深度及淋巴结转移有关(F=5.77,t=-5.650、6.445,P<0.01、0.001);E-cadherin阳性表达率与病人年龄无关(X~2=1.051,P>0.05),而与病理分级、手术-病理分期、子宫肌层浸润深度及淋巴结转移均有关(X~2=7.572、10.48、4.389、6.098,P<0.05、0.01)。子宫内膜腺癌中COX-2蛋白的表达与Ki-67呈正相关(r_s=0.344,P<0.01),与Caspase-3及E-cadherin呈负相关(r_s=-0.249、-0.264,P<0.05),子宫内膜腺癌中COX-2蛋白表达阳性组MVD值显著高于阴性组,差异有统计学意义(t=2.666,P<0.01);子宫内膜腺癌中Caspase-3蛋白的表达与Ki-67呈负相关(r_s=-0.241,P<0.05),E-cadherin的表达与Ki-67呈负相关(r_s=-0.277,P<0.05),子宫内膜腺癌中Ki-67阳性组MVD值显著高于Ki-67阴性组,差异有统计学意义(t=2.522,P<0.05)。结论:在子宫内膜腺癌的发生发展中COX-2、Ki-67、Caspase-3、CD34和E-cadherin可能起重要作用;COX-2表达与子宫内膜腺癌侵袭和转移关系密切,Ki-67、Caspase-3、CD34和E-cadherin可能是COX-2表达调控的重要因子;检测COX-2有助于评估子宫内膜腺癌的生物学行为及预后,指导临床制定合理的治疗方案;COX-2在肿瘤的抗侵袭转移治疗方面具有潜在的应用价值。
【Abstract】 AIMS:To investigate the relationship between the expression of COX-2,Ki-67, Caspase-3,CD34 and E-cadherin in endometrial adenoearcinoma and clinical parameter and expound the function of them in the genesis and development endometrial adenocarcinoma,and the correlation among them in endometrial adenocarcinoma.METHODS:The expression of COX-2、Ki-67、Caspase-3、CD34 and E-cadherin was measured by immunohistochemical Envision method in 20 cases of normal endometrium and 70 cases of endometrial adenocarcinoma.RESULTS:The positive expression rate of COX-2,Ki-67 protein or MVD value in the endometrial adenocarcinoma was significantly higher than that in the normal endometrium(Hc=22.17、27.81,P=0.0000, t=12.67,P<0.001),while that of Caspase-3 or E-cadherin in the adenocarcinoma was markedly lower than that in the normal endometrium(Uc=-5.097,X~2=18.79,P<0.001).The expression of COX-2 was not correlated with the patient’s age,pathological grade and clinical stage(Hc=1.050、5.566、5.358,P>0.05),but correlated with the myometrial invasion and lymph node metastasis(Uc=3.015、5.237,P<0.01).There was no relationship between Ki-67 protein expression and the patient’s age and clinical stage (Hc=3.590,5.880,P>0.05),but it was related to pathological grade,myometrial invasion and lymph node metastasis(Hc=8.504,Uc=2.514、2.963,P<0.05、0.01).The expression of Caspase-3 did not correlate with patient’s age,clinical stage,myometrial invasion,and lymph node metastasis(Uc=1.273,Hc=4.371,Uc=-1.374、1.077,P>0.05),but it correlated with pathological grade(Hc=7.320,P<0.05).There was no relationship between the value of MVD and patient’s age,pathological grade(t=1.673, F=2.09,P>0.05),but it was related to clinical stage,myometrial invasion and lymph node metastasis(F=5.77,t=5.650、6.445,P<0.01、0.001).The expression of E-cadherin did not correlate with patient’s age(X~2=11051,P>0.05),but it correlated with pathological grade,clinical stage,myometrial invasion and lymph node metastasis (X~2=7.572、10.48、4.389、6.098、P<0.05、0.01,respectively).Expression of COX-2 was correlated positively with Ki-67,MVD(r_s=0.344,P<0.01;t=2.666,P<0.05), and negatively with Caspase-3 and E-cadherin(r_s=-0.249、-0.264,P<0.05);Expression of Ki-67 was correlated positively with MVD(t=2.522,P<0.05),and negatively with Caspase-3 and E-cadherin(r_s=-0.241、-0.277,P<0.05).CONCLUSIONS:COX-2、Ki-67、Caspase-3、CD34 and E-cadherin may play important roles in the genesis and development of endometrial adenocarcinoma.COX-2 expression is closely related to the infiltration and metastasis of endometrial adenocarcinoma,Ki-67、Caspase-3、CD34 and E-cadherin were major regulators in the passway of COX-2 expression.Detection of COX-2 may be useful for evaluating the biological behavior and prognosis of endometrial adenocarcinoma,and for establishing suitable therapeutic scheme.COX-2 has potential value in anti neoplastic therapy.
【Key words】 COX-2; Ki-67; Caspase-3; MVD; E-cadherin; endometrial neoplasms; immunohistochemistry;