Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: A narrative review

Abstract

Colorectal cancers (CRCs) with high microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) show molecular and clinicopathological characteristics that differ from those of proficient mismatch repair/microsatellite stable CRCs. Despite the importance of MSI-H/dMMR status in clinical decision making, the testing rates for MSI and MMR in clinical practice remain low, even in high-risk populations. Additionally, the real-world prevalence of MSI-H/dMMR CRC may be lower than that reported in the literature. Insufficient MSI and MMR testing fails to identify patients with MSI-H/dMMR CRC, who could benefit from immunotherapy. In this article, we describe the current knowledge of the clinicopathological features, molecular landscape, and radiomic characteristics of MSI-H/dMMR CRCs. A better understanding of the importance of MMR/MSI status in the clinical characteristics and prognosis of CRC may help increase the rates of MMR/MSI testing and guide the development of more effective therapies based on the unique features of these tumors.

Keywords: characteristics; colorectal cancer; deficient mismatch repair; high microsatellite instability; microsatellite instability; prognosis; review; therapy development.

Figure 1

Flow diagram showing the molecular classification and frequency of sporadic and hereditary MSI-H/dMMR CRC. CRC, colorectal cancer; dMMR, deficient mismatch repair; MMR, mismatch repair; MSI-H, microsatellite instability-high.

Figure 2

Proposed relationship between tumor features, molecular profiles, clinicopathological characteristics, and immunological features of colorectal cancer according to MSI subtype. CIMP, CpG island methylator phenotype; CIN, chromosomal instability; dMMR, mismatch repair deficient; ECM, extracellular matrix; EMT, epithelial–mesenchymal transition; JAK/STAT, Janus kinase/signal transducer and activator of transcription; MSI, microsatellite instability; MSS, microsatellite stable; pMMR, MMR proficient; TGF, transforming growth factor; TIL, tumor-infiltrating lymphocyte; TMB, tumor mutational burden; Tregs, T-regulatory cells; VEGF, vascular endothelial growth factor.