谢雯莹, 贺洋, 傅晓, 王辉, 吴灿, 张大川, 李青. 肺腺癌相关组织学特征与PD-L1表达EGFR基因突变类型的关系[J]. 中国肿瘤临床, 2022, 49(15): 769-774. DOI: 10.12354/j.issn.1000-8179.2022.20220096
引用本文: 谢雯莹, 贺洋, 傅晓, 王辉, 吴灿, 张大川, 李青. 肺腺癌相关组织学特征与PD-L1表达EGFR基因突变类型的关系[J]. 中国肿瘤临床, 2022, 49(15): 769-774. DOI: 10.12354/j.issn.1000-8179.2022.20220096
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Wenying Xie, Yang He, Xiao Fu, Hui Wang, Can Wu, Dachuan Zhang, Qing Li. Relationship between histological characteristics and PD-L1 expression, EGFR gene mutation type in lung adenocarcinoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2022, 49(15): 769-774. DOI: 10.12354/j.issn.1000-8179.2022.20220096
Citation: Wenying Xie, Yang He, Xiao Fu, Hui Wang, Can Wu, Dachuan Zhang, Qing Li. Relationship between histological characteristics and PD-L1 expression, EGFR gene mutation type in lung adenocarcinoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2022, 49(15): 769-774. DOI: 10.12354/j.issn.1000-8179.2022.20220096
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肺腺癌相关组织学特征与PD-L1表达EGFR基因突变类型的关系

Relationship between histological characteristics and PD-L1 expression, EGFR gene mutation type in lung adenocarcinoma

    摘要
  • 摘要:
      目的  探讨非小细胞肺癌（non-small cell lung cancer，NSCLC）中肺腺癌不同组织学亚型、气道播散、胸膜侵犯等预后相关因素与程序性死亡因子配体−1（programmed death factor ligand-1，PD-L1）蛋白的表达、表皮生长因子受体（epidermal growth factor receptor，EGFR）基因的突变类型的差异分析，为精准治疗提供依据。
      方法  收集2018年1月至2020年12月苏州大学附属第三医院病理确诊肺腺癌患者233例的临床病理资料，使用免疫组织化学染色方法观察肺癌组织内PD-L1表达，同时采用扩增阻滞突变系统（amplification refractory mutation system，ARMS）法对EGFR基因片段进行检测。
      结果  233例肺腺癌中PD-L1表达阳性38.2%（89/233），在男性、年龄≥65岁、低分化、肿瘤最大直径≥2 cm以及发生淋巴结转移、气道播散和脉管、胸膜侵犯患者中阳性率较高（P<0.05）；EGFR突变阳性率70.8%（165/233），与患者性别显著相关（P<0.05）；PD-L1表达和EGFR突变交叉阳性/交叉阴性与肿瘤的侵袭能力显著相关（P<0.05）；PD-L1表达与贴壁结构、微乳头结构及实体型结构显著相关（均P<0.05），而EGFR基因突变状态与乳头结构、实体型结构相关（均P<0.05）。Pearson相关分析显示PD-L1比例与贴壁结构呈负相关（r=−0.252，P<0.001），与微乳头结构和实体型结构呈正相关（r=0.271，r=0.473，均P<0.001），与腺泡结构及乳头结构无相关性。PD-L1表达与EGFR中Exon19 Del突变有显著的相关性（P<0.001），研究发现无EGFR Exon19 Del突变的患者其PD-L1表达较高。
      结论  肺腺癌患者PD-L1表达与肿瘤的组织学结构的比例构成、分化程度、气道播散及脉管、胸膜侵犯等预后较差因素显著相关，且PD-L1表达与EGFR Exon19 Del突变显著相关，无Exon19 Del突变患者将有可能成为PD-L1抑制剂免疫治疗的优势人群，从而为临床诊疗评判提供更为可靠的科学依据。

     

    Abstract:
      Objective  To investigate prognostic factors related to different histological subtypes, airway spread, pleural invasion, programmed death-ligand 1 (PD-L1) protein expression, and epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC).
      Methods  Clinicopathological data of 233 patients with lung adenocarcinoma confirmed based on pathology findings in The Third Affiliated Hospital of Soochow University from January 2018 to December 2020 were collected. Combined with the morphological characteristics observed on H & E sections using light microscopy, the expression of programmed death-ligand 1 (PD-L1) (PD-L1 IHC 22C3 pharmDx) in lung cancer tissue was observed using immunohistochemical staining, and the EGFR gene fragment was detected using the amplification refractory mutation system (ARMS).
      Results  PD-L1 expression was positive in 89 patients with lung adenocarcinoma (38.2%). The positive rate was higher in males; those aged ≥65 years; and those with poor differentiation, maximum tumor diameter ≥2cm, lymph node metastasis, airway spread, and pleural vascular invasion (P<0.05). The positive rate of EGFR mutation was 70.8%, which was significantly correlated with sex (P<0.05). Furthermore, PD-L1 expression and EGFR mutation double positive or double negative were significantly correlated with the invasive ability of tumors (P<0.05). PD-L1 expression was significantly correlated with adherent, micronipple, and solid structures (P<0.05), while the mutation status of the EGFR gene was related to nipple and solid structures (P<0.05). Pearson correlation analysis showed that the expression of PD-L1 was negatively correlated with adherent structure (r=-0.252, P<0.001), and positively correlated with micropapilla and solid structures (r=0.271, r=0.473, P<0.001). PD-L1 had no correlation with acinar and nipple structures. There was a significant correlation between PD-L1 expression and Exon19 Del mutations in EGFR genes (P<0.001), and PD-L1 expression was higher in patients without EGFR Exon19 Del mutation.
      Conclusions  PD-L1 expression in patients with lung adenocarcinoma is significantly correlated with poor prognostic factors such as histological structure, differentiation, airway dissemination, and pleural vascular invasion. Moreover, PD-L1 expression is significantly correlated with EGFR Exon19 Del mutation. Therefore, patients without Exon19 Del mutation may become the dominant population receiving immunotherapy with PD-L1 inhibitors. These would provide a more reliable scientific basis for clinical diagnosis and treatment.

     

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