FOXP3^(+)肿瘤浸润性淋巴细胞与乳腺癌病理特征和预后的相关性研究

Association of FOXP3^(+)tumor infiltrating lymphocytes with poor prognosis of primary breast cancer:a retrospective cohort study

目的探讨FOXP3^(+)肿瘤浸润性淋巴细胞(TILs)与乳腺癌临床病理特征之间的相关性及其预后的意义。方法选取2009年1月至2013年5月期间首都医科大学附属北京世纪坛医院治疗的156例浸润性乳腺癌患者,采用免疫组化方法检测FOXP3^(+)和CD4^(+)的蛋白表达,记录患者的年龄、肿瘤大小、肿瘤分期、淋巴结转移情况、组织学分级、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER-2)、Ki-67指数、无病生存(DFS)率和总生存(OS)率,探讨FOXP3^(+)TILs与临床病理特征之间的相关性,使用Kaplan-Meier曲线和Cox比例风险模型进行生存分析。结果156例浸润性乳腺癌患者的中位年龄为51岁(32~70岁),乳腺癌组织中,FOXP3^(+)高表达的患者51例(32.7%),FOXP3^(+)的表达在肿瘤的组织学分级(P=0.021)、PR(P=0.016)、HER-2(P=0.018)、Ki-67指数(P=0.042)、腋窝淋巴结转移(P=0.001)方面的差异均有统计学意义。CD4^(+)TILs的表达与所有患者的临床病理特征均无明显相关性。生存分析显示,FOXP3^(+)高表达患者的OS率低于FOXP3^(+)低表达患者的OS率(64.7%比87.6%,χ^(2)=15.3,P<0.001)。FOXP3^(+)高表达患者的DFS率也低于低表达患者的DFS率(56.9%比80.0%,χ^(2)=13.1,P<0.001),差异有统计学意义。在74例腋窝淋巴结转移阳性的患者中,FOXP3^(+)高表达患者的DFS率低于FOXP3^(+)低表达患者的DFS率,差异有统计学意义(χ^(2)=5.730,P<0.001)。在多因素Cox生存分析显示,FOXP3^(+)TILs是乳腺癌患者OS[HR=2.732(95%CI=1.174~6.207),P=0.023]和DFS[HR=2.092(95%CI=1.068~4.088),P=0.032]预后不良的独立影响因素。结论FOXP3^(+)高表达患者的OS率和DFS率均低于FOXP3^(+)低表达患者,FOXP3^(+)TILs可作为乳腺癌患者的独立不良预后因素。

Objective To detect the expression of FOXP3^(+)TILs in primary invasive breast cancer,analyze the correlation between the expression level of FOXP3^(+)TILs and the clinicopathological characteristics of breast cancer,and explore the relationship between FOXP3^(+)TILs and the prognosis of breast cancer.Method Surgically resected samples from 156 patients with invasive breast cancer(BC)were assessed for the expression of FOXP3^(+)TILs and CD4^(+)TILs by immunohistochemistry.The correlation between FOXP3^(+)TILs and the patients'clinicopathological characteristics was explored.Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the correlation between FOXP3^(+)TILs and breast cancer-specific survival,and to stratify the evaluation of breast cancer subtypes.Result Elevated FOXP3^(+)TILs infiltration were significantly correlated with high histological grade(P=0.021),positive human epidermal growth factor receptor-2(HER-2)(P=0.018),Progesterone receptor expression(PR)(P=0.016),high Ki-67 index(P=0.042)and axillary lymph node metastases(P=0.001).There was no significant correlation between CD4^(+)TILs expression and the clinicopathological features of all patients.Tumors with concomitant high expressions of FOXP3^(+)TILs had worse overall survival(OS)and disease-free survival(DFS)(64.7%vs 87.6%,χ^(2)=15.3,P<0.001;56.9%vs 80.0%,χ^(2)=13.1,P<0.001).The patients with axillary lymph node metastases with the high expressions of FOXP3^(+)TILs infiltration had worse DFS(P<0.001).Multivariate analysis showed that FOXP3^(+)TILs was independent predictors of OS(HR=2.732,95%CI=1.174~6.207,P=0.023)and DFS(HR=2.092,95%CI=1.068~4.088,P=0.032).Conclusion The high expression of FOXP3^(+)TILs in breast cancer is associated with tumor progression,higher expression of FOXP3^(+)TILs indicates wores OS and DFS,FOXP3^(+)TILs maybe a prognostic marker for breast cancer.