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The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis.

ABSTRACT: Background:The clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival. Methods:Patients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system. Results:A total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively). Conclusions:dMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

SUBMITTER: Guan WL

PROVIDER: S-EPMC8655239 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis.

Guan Wen-Long WL Ma Yue Y Cui Yue-Hong YH Liu Tian-Shu TS Zhang Yan-Qiao YQ Zhou Zhi-Wei ZW Xu Jian-Ying JY Yang Li-Qiong LQ Li Jia-Yu JY Sun Yu-Ting YT Xu Rui-Hua RH Wang Feng-Hua FH Qiu Miao-Zhen MZ

Frontiers in oncology 20211125

<h4>Background</h4>The clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.<h4>Methods</h4>Patients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathologica ...[more]

PMID: 34900669

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Project description:IntroductionTo date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer.Materials and methodsPatients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival.ResultsIn total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively).ConclusionIn conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.

Project description:Background: Deficient mismatch repair (dMMR) or the microsatellite instability (MSI) phenotype occupied approximately 15-18% of CRC patients. Previous studies showed that dMMR/MSI status is a favorable prognostic factor for stage II/III CRC patients. For metastatic colorectal cancer (mCRC) patients, only 5% of patients have the dMMR/MSI-H phenotype. The relationship between dMMR/MSI, chemosensitivity and survival in mCRC patients of real-world is still not clear. Materials and methods: In this study, we enrolled 77 dMMR/MSI-H mCRC patients and compared their clinicopathological characteristics with those of 510 proficient MMR (pMMR) or microsatellite stable (MSS) mCRC patients. With propensity score matching (PSM) analysis, we further compared the chemosensitivity and survival of dMMR/MSI-H mCRC patients with pMMR/MSS patients. We also analyzed the efficacy of different chemotherapy and target therapy in the dMMR/MSI-H population. Results: In PSM cohort, the objective response rate (ORR) of mCRC patients with dMMR/MSI-H undergoing first-line palliative chemotherapy was 35.2%, which was similar with patients with pMMR/MSS (35.4%, p = 1.00). The median progression-free survival (PFS) of first-line chemotherapy was significantly different (dMMR/MSI-H vs pMMR/MSS = 7.4 months vs 10.2 months; HR = 0.74; 95%CI, 0.57-0.98; p = 0.03). Overall survival (OS) of patients did not significantly differ by status (dMMR/MSI-H vs pMMR/MSS = 40.0 months vs 41.3 months; HR = 1.09; 95%CI, 0.74-1.59; p = 0.68). For second-line palliative chemotherapy, there was no difference in ORR (p = 0.53) or in PFS (HR = 0.88; 95%CI, 0.59-1.33; p = 0.56) between dMMR/MSI-H and pMMR/MSS tumors. We also found that in the overall cohort, the ORR of patients who received oxaliplatin-based and irinotecan-based chemotherapy were 28.8% and 54.5%, respectively, which were not significantly different (p = 0.16). Our results also showed that the use of bevacizumab could lead to a significantly higher ORR in dMMR/MSI-H mCRC patients compared to chemotherapy alone (55.0% vs 22.2%; p = 0.02), whereas cetuximab could not. Conclusion: The dMMR/MSI-H is not a prognostic factor for mCRC patients but is correlated with shorter PFS to first-line palliative chemotherapy.

Dataset Information

The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis.

Publications

The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis.

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