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. 2023 Jan:7:e2200179.
doi: 10.1200/PO.22.00179.

The Prevalence and Prognosis of Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Adenocarcinomas in the United States

Catherine Gutierrez  1   2 , Shuji Ogino  1   3 , Jeffrey A Meyerhardt  1   4 , J Bryan Iorgulescu  5
Affiliations

The Prevalence and Prognosis of Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Adenocarcinomas in the United States

Catherine Gutierrez et al. JCO Precis Oncol. 2023 Jan.

Abstract

Purpose: Microsatellite instability (MSI) and DNA mismatch repair (MMR) status is an indispensable biomarker in the management of colorectal cancers. We therefore examined the epidemiology of MSI-high/MMR-deficient colorectal cancers in the United States.

Methods: Adults presenting with colorectal adenocarcinoma in 2018-2019 were identified from the US National Cancer Database. Attributes associated with MSI-high/MMR-deficiency were identified using multivariable logistic regression and reported using average adjusted probabilities (%AAP) and 99.9% CIs. As a secondary aim, the survival associated with MSI/MMR status was assessed.

Results: Among 101,259 colorectal adenocarcinomas in 2018-2019, 82.0% were microsatellite stable/MMR-proficient, 3.8% MSI-low, and 14.2% MSI-high/MMR-deficient-including 16.6%, 19.9%, 12.4%, and 7.3% of stage I, II, III, and IV cancers, respectively. In locoregional cancers, MSI-high/MMR-deficiency was associated with a bimodal age distribution, female sex, right-sided colonic origin, wild-type KRAS, and a prior diagnosis of cancer (all P < .001). By race/ethnicity, colorectal adenocarcinomas were MSI-high/MMR-deficient in 16.9%AAP of non-Hispanic White (99.9% CI, 16.5 to 17.4) patients, compared with 11.3%AAP of non-Hispanic Black (99.9% CI, 10.3 to 12.4), 12.4%AAP of Asian/Pacific Islander (99.9% CI, 10.5 to 14.3), and 15.1%AAP of Hispanic (99.9% CI, 13.4 to 16.7) patients (all P < .001). Histologically, MSI-high/MMR-deficiency was associated with increasing grade, from 11.3%AAP of well-differentiated tumors (99.9% CI, 10.2 to 12.4) to 28.4%AAP of poorly differentiated cases (99.9% CI, 27.1 to 29.8; P < .001). Compared with conventional histology (15.2%AAP, 99.9% CI, 14.8 to 15.6), medullary (41.1%AAP, 99.9% CI, 33.0 to 49.3; P < .001) and mucinous (24.6%AAP, 99.9% CI, 22.8 to 26.3; P < .001) subtypes-but not signet-ring cell histology (15.5%AAP, 99.9% CI, 11.6 to 19.4; P = .79)-were more frequently MSI-high/MMR-deficient when adjusting for clinicopathologic features including grade.

Conclusion: Our findings establish the epidemiology, features, and prognostic implications of MSI-high/MMR-deficiency among colorectal adenocarcinoma patients in the United States.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Jeffrey A. Meyerhardt

Honoraria: Cota Healthcare, Merck

Research Funding: Boston Biomedical (Inst)

J. Bryan Iorgulescu

Consulting or Advisory Role: AstraZeneca

No other potential conflicts of interest were reported.

References

    1. Vilar E, Gruber SB: Microsatellite instability in colorectal cancer—the stable evidence. Nat Rev Clin Oncol 7:153-162, 2010 - PMC - PubMed
    1. Sepulveda AR, Hamilton SR, Allegra CJ, et al. : Molecular biomarkers for the evaluation of colorectal cancer: Guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol 35:1453-1486, 2017 - PubMed
    1. Le DT, Uram JN, Wang H, et al. : PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509-2520, 2015 - PMC - PubMed
    1. Overman MJ, McDermott R, Leach JL, et al. : Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study. Lancet Oncol 18:1182-1191, 2017 - PMC - PubMed
    1. Marabelle A, Le DT, Ascierto PA, et al. : Efficacy of Pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 38:1-10, 2020 - PMC - PubMed

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