程序性死亡配体1(PD-L1)表达是晚期肺腺癌中针对程序性死亡1/PD-L1的免疫疗法反应的预测性生物标志物。这项研究的目的是探讨PD-L1表达与临床病理特征之间的关系。预后,以及肺腺癌患者的驱动癌基因改变。
我们评估了1,005例手术切除的肺腺癌标本中的PD-L1表达,通过免疫组织化学使用22C3抗体。PD-L1阳性根据组织微阵列上染色的肿瘤细胞(TPS)的比例定义:<1%(阴性),1-49%(弱正),≥50%(强阳性)。PD-L1表达与临床病理特征的相关性,预后,和驱动癌基因(EGFR,KRAS,ALK,分析了ROS1和RET)在肺腺癌中的改变。
在1,005例肿瘤的726例(72%)中,PD-L1表达为阴性,161位(16%)弱阳性,和强积极的118(12%)。男性,吸烟,血清癌胚抗原水平升高,晚期病理阶段,高级别肿瘤,主要是实体瘤,有淋巴渗透或血管或胸膜浸润的肿瘤,无EGFR突变的肿瘤,与PD-L1阴性肿瘤患者(TPS<1%)相比,具有KRAS突变的肿瘤在PD-L1阳性肿瘤患者中更为常见.PD-L1阳性与ALK无关,ROS1或RET融合状态。尽管PD-L1阳性与所有患者的总体生存率低和无复发生存率低相关,在多变量分析中校正预后因素后,该结果无统计学意义.在根据驱动癌基因改变的亚组分析中,PD-L1阳性仅在EGFR突变肿瘤患者中与无复发生存不良相关。
手术切除的PD-L1表达增加的肺腺癌是经常发生在男性吸烟者中的生物学侵袭性肿瘤。PD-L1表达及其预后意义因驱动癌基因改变而异。
Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker of response to immunotherapies targeting programmed death-1/PD-L1 in advanced-stage lung adenocarcinoma. The aim of this study was to investigate the associations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene alterations in patients with lung adenocarcinoma.
We evaluated PD-L1 expression in 1,005 surgically resected lung adenocarcinoma specimens, by immunohistochemistry using the 22C3 antibody. PD-L1 positivity was defined based on the proportion of stained tumor cells (TPS) on tissue microarrays: <1% (negative), 1-49% (weakly positive), and ≥ 50% (strongly positive). Correlations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene (EGFR, KRAS, ALK, ROS1, and RET) alterations in lung adenocarcinoma were analyzed.
PD-L1 expression was negative in 726 (72%) of 1,005 tumors, weakly positive in 161 (16%), and strongly positive in 118 (12%). Male sex, smoking, elevated serum carcinoembryonic antigen levels, advanced pathological stages, high-grade tumors, predominantly solid tumors, tumors with lymphatic permeation or vascular or pleural invasion, tumors without EGFR mutations, and tumors with KRAS mutations were more common in patients with PD-L1-positive tumors (TPS ≥ 1%) than in those with PD-L1-negative tumors (TPS < 1%). PD-L1 positivity was not associated with ALK, ROS1, or RET fusion status. Although PD-L1 positivity was associated with poor overall survival and poor relapse-free survival in all patients, this was not statistically significant after adjusting for prognostic factors in the multivariate analysis. In the subgroup analysis according to driver oncogene alterations, PD-L1 positivity was associated with poor relapse-free survival only in patients with EGFR-mutated tumors.
Surgically resected lung adenocarcinomas with increased PD-L1 expression were biologically aggressive tumors that frequently occurred in male smokers. PD-L1 expression and its prognostic significance differed according to driver oncogene alterations.