Association Between Deficient MSH2/MSH6 Versus MLH1/PMS2 Status and Survival Rates in Localized Colorectal Cancer: A...

To investigate the association between loss of mutS homolog (MSH) 2/MSH6 versus loss of mutL homolog 1 (MLH1)/postmeiotic segregation (PMS) 2 expression and overall survival (OS) and disease-free survival in patients with localized colorectal cancer (CRC).

The risk of developing CRC varies depends on the expression of mismatch repair proteins. However, it is unknown whether the prognosis differs accordingly.

In this retrospective study, we included a Danish cohort of patients who underwent surgery for CRC between 2009 and 2020. The Danish Colorectal Cancer Group database was used to identify patients, and patient-level data were extracted from 6 registries. Subsequently, patients with proficient mismatch repair status, with metastatic disease, who underwent emergency surgery, or who received neoadjuvant therapy were excluded. Patients were then propensity score matched in a 1:1 ratio.

A total of 3625 patients with localized deficient mismatch repair CRC were included in the study. Patients had a median age of 75 years and a median follow-up of 4.3 years. Before matching, the MSH2/MSH6 versus MLH1/PMS2 groups differed in age, sex, and comorbidities. After matching, 556 patients were included, and loss of MSH2/MSH6 was significantly associated with better OS (hazard ratio: 0.60; 95% CI: 0.37 to 0.94); however, not disease-free survival (hazard ratio: 0.84; 95% CI: 0.54 to 1.30).

In patients with localized deficient mismatch repair CRC who underwent surgery, a significant association was found between loss of MSH2/MSH6 versus loss of MLH1/PMS2 expression and OS. Thus, these patients may be a target for a differentiated follow-up strategy.