Decoding molecular, clinico-pathological, and outcome differences between early-onset (EO, <50 years) and late-onset (LO, ≥50 years) mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC): Insights from real-world data.
作者：Michela Bartolini, Yasmine Baca, Rituparna Ganguly, David de Semir, Francesca Battaglin, Yan Yang, Sneha Soni, Pooja Mittal, Sandra Algaze, Unnati Hemant Shah, Lesly Torres-Gonzalez, Andrew Elliott, Rachna T. Shroff, Joshua Millstein, Wu Zhang, Alberto Puccini, Heinz-Josef Lenz · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.2_suppl.19 · 被引用次数：1 · 研究领域：Genetic factors in colorectal cancer、Ferroptosis and cancer prognosis、Multiple and Secondary Primary Cancers
19 Background: The incidence of EO CRC is rising globally. While clinico-molecular features of EO mismatch repair proficient/microsatellite stable CRC have been described, less is known about EO dMMR/MSI-H tumors, which are highly immunogenic and may represent a biologically distinct subset. This study provides a comprehensive comparison of EO versus LO dMMR/MSI-H CRC. Methods: We retrospectively analyzed CRC samples profiled by next-generation sequencing (NGS) of DNA/RNA and immunohistochemistry (IHC) at a CLIA-certified lab (Caris Life Sciences; Phoenix, AZ). Patients (pts) with confirmed dMMR/MSI-H CRC were stratified into EO and LO cohorts. Consensus Molecular Subtypes (CMS) were determined from RNA expression profiles using a 600-gene classifier. Statistical comparisons used chi-square, Fisher’s exact or Mann-Whitney U tests with multiple-testing correction (q<0.05). Overall survival (OS) in months (mo) was estimated from insurance claims data using Cox proportional hazards models and log-rank tests. Results: Among 3,846 dMMR/MSI-H CRC cases (EO=496; LO=3,350), EO pts were more often male (65.3% vs 39.9%, p<0.001) and Hispanic (12.7% vs 7.5%, p<0.001), while LO pts were enriched for White race (71.8% vs 38.1%, p<0.001). EO tumors were more frequently left-sided or rectal compared to LO (27% vs 13% and 15% vs 5%, respectively, p<0.001). EO tumors more often showed loss of MSH2/MSH6 expression by IHC, while LO tumors more frequently demonstrated loss of MLH1...