PD-1及PD-L1在三阴性乳腺癌中差异性表达及与临床病理特征关系的研究

目的:探讨PD-1及PD-L1在三阴性乳腺癌（triple negative breast carcinoma，TNBC）中的表达情况。方法:收集158例TNBC组织标本，应用免疫组化方法进行PD-1及PD-L1的染色，观察其在TNBC中的表达情况，分析PD-1及PD-L1的表达与各项临床病理因素的关系。结果:PD-L1在TNBC肿瘤细胞及间质淋巴细胞中的表达率分别为53.2%和74.7%，PD-1在间质淋巴细胞中的表达率为64.6%；PD-L1与PD-1的表达有相关性（P＜0.05）；PD-L1及PD-1的表达与TNBC的肿瘤体积大、高组织学级别、基底样型BC（basal like breast carcinoma，BLBC）、Ki67增殖指数高及肿瘤浸润淋巴细胞（tumor infiltrating lymphocyte，TIL）高百分比相关（P＜0.05），多因素回归分析提示肿瘤的大小、BLBC、Ki67高增殖指数及TIL高百分比是PD-L1和PD-1表达的危险因素；PD-L1及PD-1在伴髓样特征的癌、伴大汗腺特征的癌及化生性癌中高表达，在浸润性小叶癌、腺样囊性癌及腺泡细胞癌中不表达。结论:PD-L1及PD-1在TNBC中高表达，可以作为TNBC免疫治疗的靶标及预后标记物；肿瘤体积大、BLBC、Ki67增殖指数高及高TIL是PD-L1及PD-1表达的危险因素；PD-L1及PD-1表达在TNBC中存在组织学异质性。

Differential expression of PD-1 and PD-L1 in triple negative breast carcinoma and its correlation with clinicopathology

Objective:To investigate the expression of PD-L1 and PD-1 in triple negative breast carcinoma (TNBC).Methods:158 TNBC tissue specimens were collected.Immunohistochemical staining was used for PD-1 and PD-L1 staining to observe the expression of PD-1 and PD-L1 in TNBC,and to analyze the relationship between the expression of PD-1,PD-L1 and various clinicopathological factors.Results:The expression rates of PD-L1 in TNBC tumor cells and interstitial lymphocytes were 53.2% and 74.7%,respectively.The expression rate of PD-1 in interstitial lymphocytes was 64.6%.there was a correlation between the expression of PD-L1 and PD-1(P＜0.05).The expressions of PD-L1 and PD-1 were correlated with larger tumor size,high histological grade,basal like breast carcinoma (BLBC),high proliferation index of Ki67 and high percentage of tumor infiltrating lymphocyte (TIL) in TNBC（P＜0.05）.Multivariate regression analysis suggested that tumor size,BLBC subtype,high proliferation index of Ki67 and high percentage of TIL were risk factors for the expression of PD-L1 and PD-1,PD-L1 and PD-1 was highly expressed in carcinoma with medullary features,carcinoma with apocrine differentiation and metaplastic carcinoma,but not in invasive lobular carcinoma,adenoid cystic carcinoma and acinar cell carcinoma.Conclusion:PD-L1 and PD-1 are highly expressed in TNBC,which can be used as targets and prognostic markers for TNBC immunotherapy.Larger tumor size,BLBC subtype,high proliferation index of Ki67 and high TIL are risk factors for PD-L1 and PD-1 expression.The expressions of PD-L1 and PD-1 are histologically heterogeneous in TNBC.