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肺腺癌亚型的分类与肿瘤细胞程序性死亡配体 1(PD-L1)表达的关联。

Association of Lung Adenocarcinoma Subtypes According to the IASLC/ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells.

机构信息

Thoracic Oncology Unit, Instituto Nacional de Cancerología, Mexico City, Mexico.

Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico.

出版信息

Pathol Oncol Res. 2021 Apr 8;27:597499. doi: 10.3389/pore.2021.597499. eCollection 2021.

Abstract

Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features. PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival. A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23-94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PD-L1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominant-papillary pattern, and 68.7% of patients with predominant-solid pattern ( = 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS. According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.

摘要

程序性死亡配体 1(PD-L1)蛋白表达是研究非小细胞肺癌(NSCLC)患者的最广泛的生物标志物之一。然而,关于其与不同腺癌亚型的关联的信息却很少。本研究根据 IASLC/ATS/ERS 分类以及其他相关组织学和临床特征评估了 PD-L1 表达的频率。通过免疫组织化学(IHC)评估 PD-L1 表达。根据肿瘤细胞膜的阳性程度,我们将患者分为三个不同的肿瘤比例评分(TPS)截断点:a)<1%(阴性),b)1%至 49%,c)≥50%;之后,我们分析了 PD-L1 表达与肺腺癌(LADC)主要亚型以及其他临床特征之间的关联。作为探索性结果,我们评估了 PD-L1 TPS 评分≥15%是否可作为确定生存的生物标志物。共有 240 例患者纳入最终分析。诊断时的中位年龄为 65 岁(范围 23-94 岁)。整个队列中观察到 52.5%的患者存在 PD-L1 TPS≥1%;关于特定的主要组织学模式,在主要表现为贴壁型的患者中,有 31.2%的患者 PD-L1 TPS≥1%,在主要表现为腺泡型的患者中,有 46.2%的患者 PD-L1 TPS≥1%,在主要表现为乳头型的患者中,有 42.8%的患者 PD-L1 TPS≥1%,在主要表现为实体型的患者中,有 68.7%的患者 PD-L1 TPS≥1%(=0.002)。另一方面,在腺癌亚型中,PD-L1 TPS≥50%的肿瘤比例无显著差异。在单变量生存分析中,PD-L1 TPS 截断值≥15%与较差的 PFS 和 OS 相关。根据 IASLC/ATS/ERS 肺腺癌分类,主要实体型与更高比例的 PD-L1 阳性样本相关,没有一个亚型与高(≥50%)TPS PD-L1 相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d3b/8262243/3591001eb14d/pore-27-597499-g001.jpg

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