Age-related incidence of mismatch repair deficiency (dMMR) and its prognostic role in BRAF-mutant colorectal cancer

Background The incidence of BRAF mutation and defective mismatch repair (dMMR) in colorectal cancer (CRC) is low. While dMMR is closely related to BRAF mutation, its prognostic significance in BRAF-mutant CRC remains unclear. Methods We conducted a single-center retrospective analysis of CRC patients with available genetic data. Patients with confirmed BRAF(V600E) mutation were included, and their clinicopathologic characteristics and MMR status were also collected. Results A total of 454 BRAF-mutant CRC cases were analyzed. BRAF-mutant CRC demonstrated a significant association with dMMR ( P < 0.001). dMMR incidence increased with age, particularly in female ( P < 0.001). Patients with dMMR tumor exhibited significantly improved disease-free survival (DFS) and overall survival (OS) (both P < 0.001). Furthermore, MMR status was identified as an independent prognostic factor for DFS ( P = 0.026). In non-metastatic cases, dMMR was associated with significantly improved DFS ( P < 0.001), and remained an independent prognostic factor for DFS ( P = 0.016), whereas no survival benefit was observed in metastatic cases. In stage III-IV BRAF-mutant CRC, dMMR correlated with improved DFS and OS ( P < 0.001, P = 0.039), and was confirmed as an independent prognostic factor for both DFS and OS ( P = 0.016, P =0.043). In contrast, no significant was found in stage I-II. Conclusion The incidence of dMMR increases significantly with age, particularly in female patients. dMMR is a favorable prognostic marker in advanced but non-metastatic BRAF-mutant CRC, suggesting its utility in guiding risk stratification and treatment decisions.