Isolated tumor cell clusters (ITC) in lymph nodes and PD-L1 expression on tumor-associated immune cells are prognostic factors for microsatellite instable-high gastric cancers
Menghan Cui , Yangli Zhou , Yin Han , Nannan Chen , Min Zhao , Yan Wang , Fengxia He
{"title":"Isolated tumor cell clusters (ITC) in lymph nodes and PD-L1 expression on tumor-associated immune cells are prognostic factors for microsatellite instable-high gastric cancers","authors":"Menghan Cui , Yangli Zhou , Yin Han , Nannan Chen , Min Zhao , Yan Wang , Fengxia He","doi":"10.1016/j.tranon.2025.102465","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Microsatellite instable-high (MSI-H) gastric cancer (GC) represents a distinct subgroup. However, controversy exists regarding the role of MSI in GCs, and the factors leading to internal prognostic differences among MSI-H GCs are rarely studied.</div></div><div><h3>Methods</h3><div>We identified 53 MSI-H cases from 941 consecutive GCs and conducted a detailed investigation of the clinical significance, clinicopathological correlations, and prognostic indicators of MSI-H GCs.</div></div><div><h3>Results</h3><div>Compared to MSI-low (MSI-L)/microsatellite stable (MSS) GCs, the MSI-H cohort was characterized by older age, female predominance, antral location, fewer lymph node (LN) metastases (H&E), and earlier tumor stage, but was also associated with larger tumor size, poor differentiation, and a high incidence of isolated tumor cell clusters (ITC) in negative LNs. ITC was then found to be correlated with tumor volume, Lauren subtype, pT stage, LN status (H&E), and lymphovascular invasion, with tumor size identified as an independent risk factor. Regarding prognosis, MSI-H GCs did not show longer survival time compared to MSI-L/MSS cases overall and in Stage Ⅲ-Ⅳ, but exhibited shorter survival time in Stage Ⅰ-Ⅱ. Moreover, in addition to age, pN stage, and distant metastasis, ITC and PD-L1 expression influenced survival in MSI-H GCs. ITC was confirmed as an independent unfavorable prognostic factor, while PD-L1 expression on interstitial immune cells independently predicted a favorable outcome.</div></div><div><h3>Conclusions</h3><div>Our results suggest that MSI-H GC represents a peculiar clinicopathological entity with frequent occurrence of ITC in negative LNs. ITC and PD-L1 are crucial prognostic indicators for MSI-H patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"59 ","pages":"Article 102465"},"PeriodicalIF":5.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523325001962","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Microsatellite instable-high (MSI-H) gastric cancer (GC) represents a distinct subgroup. However, controversy exists regarding the role of MSI in GCs, and the factors leading to internal prognostic differences among MSI-H GCs are rarely studied.
Methods
We identified 53 MSI-H cases from 941 consecutive GCs and conducted a detailed investigation of the clinical significance, clinicopathological correlations, and prognostic indicators of MSI-H GCs.
Results
Compared to MSI-low (MSI-L)/microsatellite stable (MSS) GCs, the MSI-H cohort was characterized by older age, female predominance, antral location, fewer lymph node (LN) metastases (H&E), and earlier tumor stage, but was also associated with larger tumor size, poor differentiation, and a high incidence of isolated tumor cell clusters (ITC) in negative LNs. ITC was then found to be correlated with tumor volume, Lauren subtype, pT stage, LN status (H&E), and lymphovascular invasion, with tumor size identified as an independent risk factor. Regarding prognosis, MSI-H GCs did not show longer survival time compared to MSI-L/MSS cases overall and in Stage Ⅲ-Ⅳ, but exhibited shorter survival time in Stage Ⅰ-Ⅱ. Moreover, in addition to age, pN stage, and distant metastasis, ITC and PD-L1 expression influenced survival in MSI-H GCs. ITC was confirmed as an independent unfavorable prognostic factor, while PD-L1 expression on interstitial immune cells independently predicted a favorable outcome.
Conclusions
Our results suggest that MSI-H GC represents a peculiar clinicopathological entity with frequent occurrence of ITC in negative LNs. ITC and PD-L1 are crucial prognostic indicators for MSI-H patients.
期刊介绍:
Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.