EB病毒相关淋巴上皮瘤样癌中肿瘤浸润淋巴细胞分布特征及其临床意义

Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance

目的探讨EB病毒相关淋巴上皮瘤样癌(LELC)中肿瘤浸润淋巴细胞(TIL)亚群分布特征与不同病理亚型LELC之间的关系及临床意义。方法收集2006年1月至2018年10月就诊于浙江省肿瘤医院、有足够石蜡组织样本、临床资料完整、EB病毒编码RNA阳性LELC病例;免疫组织化学染色方法检测免疫细胞分型标志物(CD20、CD138、CD4、CD8、CD56和FOXP3)。两位病理医生对HE染色切片进行复核,并对免疫组织化学结果进行判读。相关性分析评估TIL的亚群分布与病理相关特征的关系,生存分析研究其与临床预后的关系。结果入组EB病毒相关LELC 102例,其中间质富于TIL的经典型LELC(c-LELC)46例,间质相对缺乏TIL的非经典型LELC(n-LELC)56例。TIL分析结果显示,c-LELC中各亚型TIL均较丰富,其中以B淋巴细胞为优势亚群,n-LELC中TIL数量相较于c-LELC少,其中优势亚群为T淋巴细胞为主。在这两组中浆细胞分布无明显差异。生存分析发现TIL总数量、CD20^(+)B细胞、CD4^(+)T细胞和表达FOXP3的调节性T(FOXP3^(+)Treg)细胞浸润情况对LELC的总生存期(P值分别为0.004、0.003、0.008、0.025)和无病生存期(P值分别为0.011、0.003、0.038、0.041)均有显著的正向影响。结论不同形态学亚型EB病毒相关LELC具有不同的肿瘤免疫特征。c-LELC间质中总的TIL数量显著较n-LELC多,在亚群分布方面,B淋巴细胞是c-LELC的优势TIL,T淋巴细胞是n-LELC的优势TIL;LELC中TIL、CD20^(+)B细胞、CD4^(+)T细胞和FOXP3^(+)Treg细胞浸润提示更好的预后。

Objective To investigate the association between the distribution of tumor infiltrating lymphocytes(TIL)in EBV associated lymphoepitheliomatoid carcinoma(LELC)and the pathological subtypes of LELC,as well as the clinical significance of TIL distribution.Methods The LELC patients with sufficient tumor tissues,complete clinical data and positive EBER,who visited Zhejiang Cancer Hospital,Hangzhou,China from January 2006 to October 2018,were selected.Various immunohistochemical markers(CD20,CD138,CD4,CD8,CD56 and FOXP3)were examined for TIL typing.Two pathologists reviewed the hematoxylin and eosin(HE)staining sections and interpreted the immunohistochemical results.Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC′s pathological characteristics.Survival analyses were conducted to study the prognostic values of TIL subgrouping.Results A total of 102 patients with EBV related LELC were included.46 of them were classic LELC(c-LELC)with rich interstitial TIL,and 56 were non-classic LELC(n-LELC)with relatively fewer interstitial TIL.The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL,with B lymphocytes as the dominant subgroup.The number of TIL in n-LELC was fewer than that in c-LELC,with T lymphocytes as the dominant subgroup.There was no significant difference in the distribution of plasma cells between the two groups.Survival analysis showed that the total number of TIL,and the infiltrations of CD20^(+)B cells,CD4^(+)T cells,and FOXP3^(+)Treg cells were associated with better overall survivals(P=0.004,0.003,0.008 and 0.025,respectively)and disease-free survivals(P=0.011,0.003,0.038 and 0.041,respectively)in patients with LELC.Conclusions The morphologic subtypes of EBV-related LELC have different tumor immune characteristics.The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC.Interestingly,B lymphocytes are the dominant TIL in c-LELC,while T lymphocytes are the dominant TIL in n-LELC.The infiltration of TIL,CD20^(+)B cells,CD4^(+)T cells and FOXP3^(+)Treg cells in LELC may suggest a better prognosis.