三阴性乳腺癌组织PD-L1和HIF-1α表达临床意义

Clinical significance of PD-L1 and HIF-1α expression in triple negative breast cancer

目的研究三阴性乳腺癌（triple negative breast cancer，TNBC）中程序性死亡配体1（programmed death ligand-1，PD-L1）和缺氧诱导因子1α（hypoxia inducible factor-1α，HIF-1α）蛋白的表达及其与临床病理参数、生存预后的相关性。探讨二者共表达在TNBC中的预后价值。方法选取2010-01—01—2013-1231中国人民解放军福州总医院术后病理确诊为TNBC的女性患者103例，采用免疫组化法检测乳腺癌组织中PD-L1和HIF-1α表达，分析二者表达与临床病理参数及预后的相关性。结果TNBC组织中PDL1和HIF1α的阳性表达率分别为30．1％（31／103）和54．4％（56／103），二者表达呈正相关，r=0．559，P〈0．001。PD-L1表达与肿瘤大小、淋巴结转移、肿瘤分期显著相关，P〈0．05；HIF-1α表达与年龄、肿瘤大小、组织学分级、淋巴结转移、肿瘤分期显著相关，P〈0．05。Kaplan-Meier生存曲线和Log—rank分析显示，肿瘤大小、TNM分期、淋巴结转移情况及肿瘤PDL1、HIF-1α表达可影响TNBC患者的3年无病生存期（disease free survival，DFS），P〈0．05；多因素分析显示，PD-L1表达与TNM分期可能为TNBC患者的独立预后危险因素，P〈0．05。TNBC组织中PD-L1和HIF-1α不同的表达组合可影响患者的生存预后，共表达组3年DFS率显著低于PD-L1／HIF-1α单独表达阳性或PD-L1和HIF-1α均为阴性组，P〈0．00l。结论PD-L1和HIF-1α在TNBC组织中共同高表达提示预后不良，可能为TNBC治疗提供新选择。

OBJECTIVE To investigate the correlation between PD-L1/HIF 1α expression and clinicopathologic features and prognosis in patients with triple negative breast cancer（TNBC） and to observe the clinical value of their co-expression. METHODS A total of 103 eligible patients who were diagnosed by pathology in Fuzhou General Hospital,from January 1,2010 to December 31,2013 were enrolled. Immunohistochemistry was used to detect PD-L1/HIF-1α expression. RESULTS The positive rates of PEVL1 and HIF-1α expression were 30. 1% （31/103） and 54.4%（56/103）,respec tively. High PD-L1 expression was significantly correlated with that of HIF-1α（r= 0. 559, P〈0. 001）. Both PD-L1 and HIF-1α expression were correlated with larger tumor size, more positive lymph node number and advanced stage（P〈 0.05）. In addition, HIF-1α expression were also related to age and tumor grade（P〈0.05）. Survival analysis using a Ka plane-Meier survival plot with Log-Rank test identified five significant risk factors for poor 3-year disease-free survival （DFS） ：larger tumor size, advanced stage, lymph node invasion, positive PD-L1 expression and HIF-1α expression（P〈 0.05）. In multivariate analysis, advanced stage and positive PD-L1 expression were significantly associated with poor 3-year DFS（P〈0.05）. There was significant difference among different forms of Pd-L1/HIF-1α co-expression. Patients with a high expression of PD-L1/HIF 1α had the worst 3-year DFS（P〈0. 001）. CONCLUSION High co-expression of PDL1 and HIF -1α is significantly associated with a worse prognosis for TNBC patients,which may provide a novel approach for this type of patients.