乳腺浸润性导管癌中上皮间质转化相关蛋白表达与临床病理特征和预后的关系

Relation Between Epithelial Mesenchymal Transition Related Proteins Expressions and Clinicopathologic Features or Prognosis of Patients with Invasive Ductal Carcinoma of Breast

目的探讨上皮间质转化(EMT)相关蛋白在乳腺浸润性导管癌组织中的表达及其与乳腺癌患者临床病理特征及预后的关系。方法采用免疫组织化学方法检测118例乳腺浸润性导管癌患者的癌组织中及其30例相应癌旁正常乳腺组织中EMT相关蛋白Vimentin、E-cadherin、基质金属蛋白酶2(MMP2)的表达。分析EMT相关蛋白表达与乳腺浸润性导管癌患者的临床病理因素(年龄、肿瘤部位、肿瘤大小、淋巴结转移、组织学分级、TNM分期)及预后之间的关系。结果 1乳腺浸润性导管癌组织中Vimentin蛋白表达阳性率明显高于正常乳腺组织〔50.8%(60/118)比10.0%(3/30),P<0.05〕,E-cadherin蛋白表达阳性率明显低于正常乳腺组织〔56.8%(67/118)比93.3%(28/30),P<0.05〕,MMP2蛋白表达阳性率明显高于正常乳腺组织〔63.6%(75/118)比6.7%(2/30),P<0.05〕。2乳腺浸润性导管癌组织中Vimentin蛋白阳性表达与患者的淋巴结转移及TNM分期呈正相关(分别rs=0.346,P<0.05;rs=0.231,P<0.05),E-cadherin蛋白阳性表达与患者的肿瘤大小、淋巴结转移、组织学分级和TNM分期呈负相关(分别rs=-0.444,P<0.05;rs=-0.493,P<0.05;rs=-0.323,P<0.05;rs=-0.474,P<0.05),MMP2蛋白阳性表达与肿瘤大小、淋巴结转移、组织学分级和TNM分期呈正相关(分别rs=0.361,P<0.05;rs=0.434,P<0.05;rs=0.396,P<0.05;rs=0.376,P<0.05),这3个指标与其他临床病理因素无关(P>0.05)。3 Kaplan-Meier生存曲线分析结果显示,Vimentin及MMP2阳性表达越强,无瘤生存时间越短(P<0.05),E-cadherin阳性表达越强,无瘤生存时间越长(P<0.05)。结论临床通过联合检测乳腺浸润性导管癌EMT相关蛋白Vimentin、E-cadherin、MMP2可能能够预测癌病理分级和临床分期,以及有效预测浸润性导管癌患者的预后。

Objective To investigate the relationship of epithelial mesenchymal transition （EMT） related proteins expressions in invasive ductal carcinoma of breast to its clinicopathologic features and prognosis. Methods The expres- sions of EMT related proteins （Vimentin, E-cadherin, and MMP2） in the 118 cases of invasive ductal carcinoma of breast and 30 cases of corresponding normal breast tissues adjacent to cancer were detected by immunohistochemistry. The relationship of EMT related proteins expressions to age, tumor site, tumor size, lymph node metastasis, histological grade, TNM stage or prognosis of the patients with invasive ductal carcinoma of breast was analyzed. Results ① The positive rates of the Vimentin protein and MMP2 protein in the invasive ductal carcinoma of breast were significantly higher than those in the corresponding normal breast tissues adjacent to cancer [Vimentin protein： 50.8% （60/118） versus 10.0% （3/30）, P〈0.05; MMP2 protein： 63.6% （75/118） versus 6.7% （2/30）, P〈0.05 ], the positive rate of E-cadherin in the invasive ductal carcinoma of breast was significantly lower than that in the corresponding normal breast tissues adjacent to cancer 56.8% （67/118） versus 93.3% （28/30）, P〈0.05].② The positive rate of the Vimentin protein expression in the invasive ductal carcinoma tissue was positively related with the lymph node metastasis and TNM staging （rs =0.346, P〈0.05; rs = 0.231, P〈0.05）. The positive rate of the E-cadherin or MMP2 protein expression was negatively or positively related with the tumor size, lymph node metastasis, histological grade, and TNM stage （E-cadherin： rs =-0.444, P〈0.05; rs =-0.493, P〈0.05; rs =-0.323, P〈0.05; rs =-0.474, P〈0.05. MMP2： rs =0.361, P〈0.05; rs =0.434, P〈0.05; rs =0.396, P〈0.05; r, =0.376, P〈0.05）. ③ The Kaplan-Meier survival curve analysis showed that the positive expressions of Vimentin and MMP2 were stronger, the tumor free survival time was shorter （P〈0.05）, and the positive expression of E-cadherin was stronger, the tumor free survival time was longer （P〈0.05）. Conclusion Joint detection of EMT related proteins （Vimentin, E-cadherin, MMP2） of invasive ductal carcinoma tissue of breast could predict the pathological grade and clinical stage, as well as effective prognosis of patients with invasive ductal carcinoma of breast in clinical.