Department of Pathology University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Translational Molecular Pathology, The University of Texas M. D. Anderson, Houston, Texas.
J Thorac Oncol. 2024 Feb;19(2):273-284. doi: 10.1016/j.jtho.2023.09.275. Epub 2023 Sep 16.
Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment.
WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of the study cases was characterized by the HTG EdgeSeq Precision Immuno-Oncology Panel.
By WES data, 11 cases were classified as SPLC and seven cases as IPM. Two cases were technically suboptimal. Analysis revealed marked genomic and immunogenic heterogeneity, but immune gene expression profiles highly correlated with mutation profiles. Tumors classified as IPM have a large number of shared mutations (ranging from 33.5% to 80.7%). The agreement between individual morphologic assessments for each case and WES was 58.3%. One case was unanimously interpreted morphologically as IPM and was in agreement with WES. In a further 17 cases, the number of pathologists whose morphologic interpretation was in agreement with WES ranged from two (one case) to 15 pathologists (one case) per case. Pathologists showed a fair interobserver agreement in the morphologic staging of multiple LSCCs, with an overall kappa of 0.232.
Staging of multifocal LSCC based on morphologic assessment is unreliable. Comprehensive genomic analyses should be adopted for the staging of multifocal LSCC.
多灶性肺鳞状细胞癌（LSCC）的分期形态学和分子数据有限。在这项研究中，全外显子组测序（WES）被用作金标准，以确定多灶性 LSCC 是否代表单独的原发性肺癌（SPLC）或肺内转移（IPM）。基因组谱与综合形态评估进行了比较。
使用 Illumina NovaSeq6000 S4-Xp（Illumina，圣地亚哥，CA）对 20 对多灶性 LSCC 肿瘤及其配对的正常淋巴结进行 WES。WES 克隆和亚克隆分析数据由 16 位胸病理学家与组织学评估进行比较。此外，通过 HTG EdgeSeq Precision Immuno-Oncology Panel 对研究病例的免疫基因谱进行了特征描述。
根据 WES 数据，11 例被分类为 SPLC，7 例为 IPM。有两例技术上不太理想。分析显示出明显的基因组和免疫原性异质性，但免疫基因表达谱与突变谱高度相关。被归类为 IPM 的肿瘤具有大量共享突变（范围从 33.5%到 80.7%）。每个病例的个体形态评估与 WES 的一致性为 58.3%。有一个病例在形态学上一致地被解释为 IPM，并与 WES 一致。在另外 17 例中，形态学解释与 WES 一致的病理学家数量从每个病例 2 名（1 例）到 15 名（1 例）不等。病理学家在多灶性 LSCC 的形态学分期中表现出公平的观察者间一致性，总体kappa 值为 0.232。
基于形态学评估的多灶性 LSCC 分期不可靠。应采用综合基因组分析对多灶性 LSCC 进行分期。
