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Mismatch Repair Status of Gastric Cancer and Its Association with the Local and Systemic Immune Response

 Su‐Jin Shin  ;  Sang Yong Kim  ;  Yoon Young Choi  ;  Taeil Son  ;  Jae‐Ho Cheong  ;  Woo Jin Hyung  ;  Sung Hoon Noh  ;  Chung‐Gyu Park  ;  Hyoung‐Il Kim 
 ONCOLOGIST, Vol.24(9) : e835-e844, 2019 
Journal Title
Issue Date
Gastric cancer ; Microsatellite instability ; Survival ; Tumor‐infiltrating lymphocytes
BACKGROUND: Microsatellite instability (MSI)-high (MSI-H) colorectal cancer is known to be associated with increased tumor-infiltrating lymphocytes (TILs), elevated host systemic immune response, and a favorable prognosis. In gastric cancer, however, MSI status has rarely been evaluated in the context of TILs and systemic immune response. MATERIALS AND METHODS: We evaluated data for 345 patients with gastric cancer who underwent gastrectomy with MSI typing. The numbers of TILs were counted after immunohistochemical staining with anti-CD3, CD4, CD8, forkhead box P3 (Foxp3), and granzyme B to quantify the subsets of TILs. To evaluate the systemic immune response, the differential white blood cell count and prognostic nutritional index (PNI) were obtained. RESULTS: Of the 345 patients, 57 demonstrated MSI-H tumors and 288 demonstrated non-MSI-H tumors. MSI-H tumors carried significantly higher densities of CD8+ T cells, Foxp3+ T cells, and granzyme B+ T cells and a higher ratio of Foxp3/CD4 and granzyme B/CD8. The prognostic impact of TILs differed between patients with MSI-H tumors and those with non-MSI-H tumors. The TIL subsets were not found to be significant prognostic factors for recurrence-free survival (RFS) or overall survival (OS) in the MSI-H tumor group. In the non-MSI-H tumor group, multivariate analysis showed that stage, PNI, and CD4+ T cells were independent prognostic factors for RFS, and stage, PNI, and the Foxp3/CD4 ratio were independent prognostic factors for OS. CONCLUSIONS: The association between systemic/local immune response and prognosis differed according to MSI status. Different tumor characteristics and prognoses according to MSI status could be associated with the immunogenicity caused by microsatellite instability and subsequent host immune response. IMPLICATIONS FOR PRACTICE: This study demonstrates that the density of each subset of tumor-infiltrating lymphocytes (TILs) differed between microsatellite instability (MSI)-high and non-MSI-high tumors. Moreover, the prognostic effect of the preoperative systemic immune response status and TILs differed between the MSI-high (MSI-H) and non-MSI-H tumor groups. The present study may help to identify the mechanisms of cancer progression and develop treatment strategies for MSI-high gastric cancer.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Il(김형일) ORCID logo https://orcid.org/0000-0002-6134-4523
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Son, Tae Il(손태일) ORCID logo https://orcid.org/0000-0002-0327-5224
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Choi, Yoon Young(최윤영) ORCID logo https://orcid.org/0000-0002-2179-7851
Hyung, Woo Jin(형우진) ORCID logo https://orcid.org/0000-0002-8593-9214
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