不同分子亚型乳腺癌中程序性细胞死亡4的表达及其与预后的关系

Expression of Programmed Cell Death 4 in Different Subtypes of Breast Cancer and Its Relationship to Prognosis

目的探讨不同分子亚型乳腺癌中程序性细胞死亡4(PDCD4)的表达及其与预后的关系。方法收集广东省妇幼保健院乳腺科2007年1月至2009年12月期间手术切除的乳腺癌及相应的癌旁组织标本各338例,按免疫表型将其分为管腔型(199例)、HER-2阳性型(63例)及三阴型(76例),采用SP法检测不同分子亚型乳腺癌中PDCD4的表达情况,并分析其与预后的关系。用SPSS 13.0软件进行统计学分析,率的比较用卡方检验。用Kaplan-Meier法对患者的无病生存及总生存情况进行分析,用log-rank检验比较生存曲线间的差异,运用Cox分析影响各分子亚型乳腺癌生存预后的因素。结果①338例乳腺癌中PDCD4蛋白表达总阳性率为56.80%(192/338),表达缺失率为43.20%(146/338);相应癌旁正常乳腺组织中PDCD4蛋白表达总阳性率为96.44%(326/338)。其中管腔型乳腺癌中PDCD4表达阳性率明显高于HER-2阳性型(χ2=38.315,P=0.000)及三阴型(χ2=33.746,P=0.000),而HER-2阳性型及三阴型乳腺癌中PDCD4蛋白表达阳性率差异无统计学意义(χ2=0.448,P=0.503);且管腔型、HER-2阳性型及三阴型乳腺癌中PDCD4蛋白表达阳性率均分别明显低于癌旁正常组织(χ2=39.206,P=0.000;χ2=60.398,P=0.000;χ2=65.185,P=0.000)。②管腔型乳腺癌中PDCD4表达与年龄、组织学分级、T分期及N分期均有关(χ2=3.979,P=0.046;χ2=13.826,P=0.001;χ2=12.604,P=0.002;χ2=28.613,P=0.000);HER-2阳性型乳腺癌中PDCD4表达与年龄及T分期无关(χ2=0.033,P=0.856;χ2=4.258,P=0.119),而与组织学分级及N分期有关(χ2=9.972,P=0.007;χ2=13.714,P=0.003);三阴型乳腺癌中PDCD4表达与年龄及T分期无关(χ2=0.817,P=0.366;χ2=0.990,P=0.610),而与组织学分级及N分期有关(χ2=14.269,P=0.001;χ2=7.945,P=0.047)。③338例乳腺癌中PDCD4蛋白阳性表达者其无病生存及总生存均明显优于PDCD4蛋白阴性表达者(P=0.000,P=0.000),且在各分子亚型乳腺癌中,同样显示出PDCD4蛋白阳性表达者其无病生存及总生存明显优于PDCD4蛋白阴性表达者(P=0.000,P=0.000)。④多因素分析显示,影响乳腺癌无病生存的独立因素包括T分期、N分期及PDCD4表达(P=0.004,P=0.001,P=0.000),影响乳腺癌总生存的独立因素包括组织学分级、T分期、N分期及PDCD4表达。结论 PDCD4在乳腺癌中表达下调,其中三阴型及HER-2阳性型乳腺癌中下调更明显;PDCD4蛋白阳性表达者无病生存及总生存均明显优于PDCD4蛋白阴性表达者,PDCD4可作为预测乳腺癌预后的独立因素。

Objective To explore the expression of programmed cell death 4 （PDCD4） in different subtype of breast cancer and its relationship to prognosis. Methods Three hundred and thirty-eight patients with breast cancer from January 2007 to December 2009 in this hospital were collected. All these patients were categorized into three subtypes which was luminal, HER-2 positive, and triple negative according to the results of stain. SP immtmo- histochemistry was used to detect the expression of PDCD4 in the different subtype of breast cancer. Kaplan-Meier and Cox proportional hazards model was used to analyze the prognosis. Results ①The positive rate of PDCD4 expression was 73.37% （146/199）, 30. 16% （19/63）, and 35.53% （27/76） in the luminal, HER-2 positive, and triple negative breast cancer, respectively. The expression of PDCD4 was downregulated especially in the HER-2 positive and triple negative breast cancer（χ2=38.315, P=0. 000; Z2=33.746, P=-0. 000） as compared with the luminal breast cancer. ②The disease free survival and overall survival rates in the PDCD4 positive patients were significantly higher than those in the PDCD4 negative patients （P〈0. 05） despite the subtypes. ②Cox model revealed that T staging, N staging, and PDCD4 were the independent prognostic factors for disease free survival and that histological grade, T staging, N staging, and PDCD4 were the independent prognostic factors for overall survival. Conclusions PDCD4 expression is downregulated in all subtypes of breast cancer especially in HER-2 positive and triple negative breast cancer, and the loss of PDCD4 expression is correlated to poor prognosis. PDCD4 is an independent prognostic factor of breast cancer.