Deficient Mismatch Repair Represents a Distinct Molecular Feature of Early-Onset Colorectal Cancer in Chinese Single-Center Cohort.

Immunohistochemistry of the four mismatch repair proteins (products of MLH1, PMS2, MSH2, MSH6) plus microsatellite instability status, used as the entry filter towards Lynch syndrome.

Early-onset colorectal cancer, diagnosed before age 50, is rising worldwide and in China, yet its clinicopathological features and mismatch repair status there remained poorly characterised. The authors reviewed 23,414 colorectal neoplasia cases diagnosed at a Chengdu hospital between November 2008 and June 2023, retaining 4,159 colorectal cancers with complete immunohistochemistry of the four mismatch repair proteins, and compared early-onset with late-onset disease, stratified by documented family history. Early-onset tumours showed less favourable features, including more poorly differentiated tumours, T4 stage, nodal involvement and advanced TNM stage, together with a significantly higher prevalence of deficient mismatch repair. On multivariable analysis, early-onset status was independently associated with deficient mismatch repair in the whole cohort (adjusted OR 2.27; 95% CI 1.60-3.22; p < 0.001) and among patients without documented family history (adjusted OR 1.95; 95% CI 1.33-2.86; p < 0.001), with patterns of protein loss differing by family history status.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Deficient mismatch repair is not Lynch syndrome: no germline confirmation is reported here and the contribution of somatic MLH1 promoter hypermethylation remains undetermined, which caps the reach of the work. What this cohort specifically adds is that documented family history does not discriminate deficient tumours in young patients, the association persisting in those without any: one more argument for systematic immunohistochemical screening independent of family history, including where it is not yet routine. The single-centre retrospective design, in a cohort already selected for MMR testing, precludes transposing the raw prevalence figures.

Analysis by Dr Thibaut Benquey