Epidemiology of Microsatellite Instability High (MSI-H) and Deficient Mismatch Repair (dMMR) in Solid Tumors: A Structured Literature Review

Abstract

Background. Given limited data on the epidemiology of MSI-H and dMMR across solid tumors (except colorectal cancer (CRC)), the current study was designed to estimate their prevalence. Materials and Methods. A structured literature review identified English language publications that used immunohistochemistry (IHC) or polymerase chain replication (PCR) techniques. Publications were selected for all tumors except CRC using MEDLINE, EMBASE, and Cochrane databases and key congresses; CRC and pan-tumor genomic publications were selected through a targeted review. Meta-analysis was performed to estimate pooled prevalence of MSI-H/dMMR across all solid tumors and for selected tumor types. Where possible, prevalence within tumor types was estimated by disease stages. Results. Of 1,176 citations retrieved, 103 and 48 publications reported prevalence of MSI-H and dMMR, respectively. Five pan-tumor genomic studies supplemented the evidence base. Tumor types with at least 5 publications included gastric (n = 39), ovarian (n = 23), colorectal (n = 20), endometrial (n = 53), esophageal (n = 6), and renal cancer (n = 8). Overall MSI-H prevalence (with 95% CI) across 25 tumors was based on 90 papers (28,213 patients) and estimated at 14% (10%–19%). MSI-H prevalence among Stage 1/2 cancers was estimated at 15% (8%–23%); Stages 3 and 4 prevalence was estimated at 9% (3%–17%) and 3% (1%–7%), respectively. Overall, dMMR prevalence across 13 tumor types (based on 54 papers and 20,383 patients) was estimated at 16% (11%–22%). Endometrial cancer had the highest pooled MSI-H and dMMR prevalence (26% and 25% all stages, respectively). Conclusions. This is the first comprehensive attempt to report pooled prevalence estimates of MSI-H/dMMR across solid tumors based on published data. Prevalence determined by IHC and PCR was generally comparable, with some variations by cancer type. Late-stage prevalence was lower than that in earlier stages.