河北医科大学学报 ›› 2022, Vol. 43 ›› Issue (9): 1014-1019,1024.doi: 10.3969/j.issn.1007-3205.2022.09.005

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LAG-3及肿瘤浸润淋巴细胞在食管鳞状细胞癌患者预后中的作用

  

  1. 1. 河北医科大学第四医院病理科，河北 石家庄 050011；2. 河北医科大学第四医院肿瘤研究所，河北 石家庄 050011；3. 河北省廊坊市中医医院体检中心，河北 廊坊 065000



  • 出版日期:2022-09-25 发布日期:2022-10-02
  • 作者简介:刘尧（1987-），男，河北石家庄人，河北医科大学第四医院主治医师，医学硕士，从事肿瘤病理诊断研究。
  • 基金资助:
    国家自然科学基金项目（81871922）；河北省医学科学研究课题计划（20211159）

Role of LAG-3 and tumor infiltrating lymphocytes in the prognosis of patients with esophageal squamous cell carcinoma

  1. 1.Department of Pathology, the Fourth Hospital of Hebei Medical University,  Shijiazhuang 050011, China; 
    2.Institute of Tumor, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China; 
    3.Physical Examination Center, Langfang Hospital of TCM, 
    Hebei Province, Langfang 065000, China

  • Online:2022-09-25 Published:2022-10-02

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摘要： 目的 探讨淋巴细胞活化基因3（lymphocyte activating gene 3,LAG-3）及肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes,TILs）在食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）中的表达及其预后价值。
方法 回顾性分析我院术前未接受治疗的60例食管鳞状细胞癌患者的苏木精-伊红染色(hematoxylin-eosin staining,HE)切片并进行
TILs HE染色判读，同时进行LAG-3免疫组织化学染色，光学显微镜下观察并进行结果判读，分析LAG-3及TILs在食管鳞状细胞癌中的表达情况，统计学分析其相关性及其在食管鳞状细胞癌患者预后中的作用。
结果 免疫组织化学结果示LAG-3在ESCC
中的阳性率为38.3%（23/60），且LAG-3只在肿瘤浸润淋巴细胞上表达，在肿瘤细胞上不表达。反转录聚合酶链反应（reverse transcription polymerase chain reaction, RT-PCR）结果显示，LAG-3在ESCC中的相对表达量高于癌旁正常食管黏膜。在60例ESCC患者中，有不同程度的肿瘤淋巴细胞浸润，其中低度TILs 21例，中度TILs 27例，高度TILs 12例。LAG-3表达与TILs、肿瘤分化程度和TNM分期显著相关。Kaplan-Meier生存分析显示，患者PFS与TNM分期、淋巴结状况、LAG-3、TILs有关，差异有统计学意义（P＜0.05）；多因素COX回归分析结果显示：患者PFS与TNM分期、LAG-3有关，差异有统计学意义（P＜0.05）。
结论 LAG-3的高表达与生存率的提高相关，并且LAG-3是一个独立的生存预测因子，提示LAG-3可能是ESCC预后的一个有用的免疫标志物。


关键词: 食管肿瘤, 癌, 鳞状细胞, 淋巴细胞活化

Abstract: ObjectiveTo investigate the expression and prognostic value of lymphocyte activating gene 3（LAG-3） and tumor infiltrating lymphocytes(TILs) in esophageal squamous cell carcinoma(ESCC). 
MethodsThe hematoxylin-eosin staining(HE) sections of 60 patients with ESCC who were not treated before operation in our hospital were analyzed retrospectively, and the TILs HE staining was interpreted. Meanwhile, immunohistochemical staining for LAG-3 was performed, and the results were observed and interpreted under the light microscope. The expression of LAG-3 and TILs in ESCC was analyzed. The correlation and their function in the prognosis of patients with ESCC were statistically analyzed. 
ResultsImmunohistochemical results showed that the positive rate of LAG-3 in ESCC was 38.3%(23/60), and LAG-3 was only expressed on TILs, but not on tumor cells. Reverse transcription polymerase chain reaction(RT-PCR) showed that the relative expression of LAG-3 in ESCC was higher than that in adjacent normal esophageal mucosa. In 60 patients with ESCC, there were different degrees of tumor lymphocyte infiltration, including 21 cases of low TILs, 27 cases of moderate TILs and 12 cases of high TILs. The expression of LAG-3 was significantly correlated with TILs, tumor differentiation and TNM stage. Kaplan Meier survival analysis showed that the PFS was related to TNM stage, lymph node status, LAG-3 and TILs, suggesting significant differences(P＜0.05). Multivariate COX regression analysis showed that the PFS was related to TNM stage and LAG-3, and the difference was statistically significant(P＜0.05). 
ConclusionThe high expression of LAG-3 is associated with the improvement of survival rate, and LAG-3 is an independent predictor of survival, suggesting that LAG-3 may be a useful immune marker for the prognosis of ESCC.


Key words: esophageal neoplasms, carcinoma, squamous cell, lymphocyte activation

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