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

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. Gutierrez et al from BWH/DFCI define the epidemiology of CRCs in the United States by MSI/MMR status [ABSTRACT FROM AUTHOR]