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

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...

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Main Authors: Menghan Cui, Yangli Zhou, Yin Han, Nannan Chen, Min Zhao, Yan Wang, Fengxia He
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325001962
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author Menghan Cui
Yangli Zhou
Yin Han
Nannan Chen
Min Zhao
Yan Wang
Fengxia He
author_facet Menghan Cui
Yangli Zhou
Yin Han
Nannan Chen
Min Zhao
Yan Wang
Fengxia He
author_sort Menghan Cui
collection DOAJ
description 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.
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spelling doaj-art-1b0ed8f5756d472e8729df33c9c7fd2e2025-08-20T03:28:38ZengElsevierTranslational Oncology1936-52332025-09-015910246510.1016/j.tranon.2025.102465Isolated tumor cell clusters (ITC) in lymph nodes and PD-L1 expression on tumor-associated immune cells are prognostic factors for microsatellite instable-high gastric cancersMenghan Cui0Yangli Zhou1Yin Han2Nannan Chen3Min Zhao4Yan Wang5Fengxia He6Department of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, ChinaDepartment of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, ChinaDepartment of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China; Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People's Hospital (The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu 611137, Sichuan, ChinaDepartment of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, ChinaDepartment of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, ChinaDepartment of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China; Corresponding authors.Department of Pathology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1936523325001962Microsatellite instability (MSI)Isolated tumor cell clusters (ITC)Programmed death-ligand 1 (PD-L1)Gastric cancerPrognosis
spellingShingle Menghan Cui
Yangli Zhou
Yin Han
Nannan Chen
Min Zhao
Yan Wang
Fengxia He
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
Translational Oncology
Microsatellite instability (MSI)
Isolated tumor cell clusters (ITC)
Programmed death-ligand 1 (PD-L1)
Gastric cancer
Prognosis
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Microsatellite instability (MSI)
Isolated tumor cell clusters (ITC)
Programmed death-ligand 1 (PD-L1)
Gastric cancer
Prognosis
url http://www.sciencedirect.com/science/article/pii/S1936523325001962
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