Thomas Quentin Dominique, Vendrell Julie Adèle, Khellaf Lakhdar, Cavaillon Sarah, Quantin Xavier, Solassol Jérôme, Cabello-Aguilar Simon
Department of Medical Oncology, Institute du Cancer de Montpellier, Montpellier University, Montpellier, France.
Oncogenic Pathways in Lung Cancer, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France.
Cancer. 2025 May 1;131(9):e35882. doi: 10.1002/cncr.35882.
Microsatellite instability (MSI) has emerged as a predictive biomarker for immunotherapy response in various cancers, but its role in non-small cell lung cancer (NSCLC) is not fully understood.
The authors used the bioinformatics tool MIAmS to assess microsatellite status from next-generation sequencing (NGS) data using a tailored microsatellite score. Immunohistochemistry (IHC) assays were also performed to evaluate the correspondence between MSI and deficient mismatch repair (dMMR) status. A retrospective analysis of 1547 lung cancer patients was conducted, focusing on those with an MSI phenotype. Clinical characteristics, co-occurring molecular alterations, tumor mutation burden (TMB), and homologous recombination deficiency (HRD) status were evaluated in this subset.
Of the 1547 patients analyzed, eight (0.52%) were identified as having MSI through MIAmS, with six (0.39%) of these cases also being dMMR on IHC. All patients with dMMR had an MS score ≥2 and a history of smoking. Most patients showed loss of MLH1 and PMS2 staining on IHC. No correlation was found between MSI status and programmed death-ligand 1 expression, although all MSI patients exhibited high TMB, averaging 21.4 ± 5.6 mutations per megabase.
MSI/dMMR in lung cancer is exceedingly rare, affecting less than 1% of cases. NGS-based analysis combined with bioinformatics tools provides a robust method to identify MSI/dMMR patients, potentially guiding immunotherapy decisions. This comprehensive approach integrates molecular genotyping and MSI detection, offering personalized treatment options for lung cancer patients. NGS-based MSI testing is emerging as the preferred method for detecting microsatellite instability in various tumor types, including rare cancers.
微卫星不稳定性（MSI）已成为多种癌症免疫治疗反应的预测生物标志物，但其在非小细胞肺癌（NSCLC）中的作用尚未完全明确。
作者使用生物信息学工具MIAmS，通过定制的微卫星评分从二代测序（NGS）数据评估微卫星状态。还进行了免疫组织化学（IHC）检测，以评估MSI与错配修复缺陷（dMMR）状态之间的对应关系。对1547例肺癌患者进行了回顾性分析，重点关注具有MSI表型的患者。在该亚组中评估了临床特征、同时发生的分子改变、肿瘤突变负荷（TMB）和同源重组缺陷（HRD）状态。
在分析的1547例患者中，有8例（0.52%）通过MIAmS被鉴定为具有MSI，其中6例（0.39%）在IHC上也为dMMR。所有dMMR患者的MS评分≥2且有吸烟史。大多数患者在IHC上显示MLH1和PMS2染色缺失。虽然所有MSI患者的TMB均较高，平均每兆碱基有21.4±5.6个突变，但未发现MSI状态与程序性死亡配体1表达之间存在相关性。
肺癌中的MSI/dMMR极为罕见，影响不到1%的病例。基于NGS的分析结合生物信息学工具提供了一种强大的方法来识别MSI/dMMR患者，可能指导免疫治疗决策。这种综合方法整合了分子基因分型和MSI检测，为肺癌患者提供个性化治疗选择。基于NGS的MSI检测正成为检测包括罕见癌症在内的各种肿瘤类型中微卫星不稳定性的首选方法。
