期刊论文详细信息
The oncologist
Mismatch Repair Status of Gastric Cancer and Its Association with the Local and Systemic Immune Response
article
Su-Jin Shin1  Sang Yong Kim2  Yoon Young Choi3  Taeil Son3  Jae-Ho Cheong3  Woo Jin Hyung3  Sung Hoon Noh3  Chung-Gyu Park5  Hyoung-Il Kim2 
[1] Department of Pathology, College of Medicine, Hanyang University;Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei University Health System;Department of Surgery, Yonsei University College of Medicine;Robot and Minimally Invasive Surgery Center, Yonsei University Health System;Translational Xenotransplantation Research Center, Seoul National University College of Medicine;Department of Microbiology and Immunology, Seoul National University College of Medicine
关键词: Gastric cancer;    Microsatellite instability;    Tumor-infiltrating lymphocytes;    Survival;   
DOI  :  10.1634/theoncologist.2018-0273
学科分类:地质学
来源: AlphaMed Press Incorporated
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【 摘 要 】

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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