程序性死亡受体1及其配体在原发肺黏液表皮样癌中的表达特点及临床意义

Expression of programmed death receptor 1 and its ligand in primary lung mucoepidermoid carcinoma and its clinical significance

目的探讨原发肺黏液表皮样癌(pulmonary mucoepidermoid carcinoma,PMC)中程序性死亡受体1(PD-1)及其配体1 (PD-L1)、配体2 (PD-L2)表达的临床意义。方法采用免疫组化法检测41例手术切除原发肺PMC组织中PD-1、PD-L1、PD-L2和CD8+T细胞表达情况,分析它们之间的相关性及与临床病理特征的关系。结果显微镜下观察PMC由表皮样细胞、中间型细胞和黏液细胞构成。免疫标志物PD-L1在41例PMC中呈阴性;所有PMC肿瘤组织中CD8+T细胞均有不同程度表达,且其表达阳性数与肿瘤大小呈负相关;PD-1+T细胞在癌组织中15例阴性,26例呈阳性表达;PD-L2均有不同程度表达,其中8例高级别黏液表皮样癌表现为表皮样细胞及中间型细胞胞膜的中等以上强度阳性表达;33例低级别黏液表皮样癌中黏液细胞为阴性、中间型细胞及表皮样细胞胞膜呈局灶阳性。单因素分析PD-L2高表达与较短的无复发生存期相关,多因素分析显示PD-L2表达可能是预测黏液表皮样癌复发的独立危险因子之一。本研究发现PDL2表达强度与PMC的组织学分级呈正相关,高级别PMC中PD-L2阳性细胞比例和染色强度综合评分明显高于低级别PMC。结论 PD-L2是PMC重要的免疫生物标志物,可能会成为预测黏液表皮样癌复发的关键因子之一,其表达综合评分情况有助于黏液表皮样癌组织学分级,对预测临床预后有一定的作用。

Objective To investigate the clinical significance of programmed death receptor 1(PD-1)and its ligand 1(PD-L1)and ligand 2(PD-L2)in primary lung mucin epidermoid carcinoma(PMC).Methods The expressions of PD-1,PDL1,PD-L2 and CD8+ T cells in 41 patients with primary lung PMC were detected by immunohistochemistry.The correlation between them and their relationship with clinicopathological features were analyzed.Results Microscopic observation of PMC consisted of epidermal-like cells,intermediate cells,and mucous cells.The immunological marker PD-L1 was negative in 41 cases of PMC;CD8+ T cells were expressed in different degrees in all PMC tumor tissues,and the positive expression number was negatively correlated with tumor size;PD-1+T cells were negative in 15 cases and positive in 26 cases.PD-L2 was expressed in different degrees.Among them,eight cases of high-grade mucoepidermoid carcinoma showed moderate or higher intensity expression of epidermal-like cells and intermediate cell membrane.In 33 cases of low-grade mucoepidermoid carcinoma,mucus cells were negative,and intermediate cells and epidermal-like cell membranes were focally positive.Univariate analysis of PD-L2 high expression was associated with shorter recurrence-free survival.Multivariate analysis showed that PD-L2 expression may be one of the independent risk factors for predicting recurrence of mucoepidermoid carcinoma.This study found that the intensity of PD-L2 expression was positively correlated with the histological grade of PMC.The proportion of PD-L2 positive cells and the comprehensive score of staining intensity in high-grade PMC was significantly higher than that of low-level PMC.Conclusion PD-L2 is an important immunobiomarker for PMC and may be one of the key factors predicting the recurrence of mucoepidermoid carcinoma.The comprehensive evaluation of its expression is helpful for histological grading of mucoepidermoid carcinoma and which has a certain predictive clinical prognosis.