Association between Deficient MSH2/MSH6 vs MLH1/PMS2 Status and Survival Rates in Localized Colorectal Cancer: A Nationwide Cohort Study

OBJECTIVE: This study investigated the association between loss of MSH2/MSH6 versus loss of MLH1/PMS2 expression and overall survival and disease-free survival in patients with localized colorectal cancer.

BACKGROUND: The risk of developing colorectal cancer varies depending on the expression of mismatch repair proteins. However, it is unknown if the prognosis differs accordingly.

METHODS: In this retrospective study, we included a Danish cohort of patients who underwent surgery for colorectal cancer between 2009 and 2020. The Danish Colorectal Cancer Group database was used to identify patients, and patient-level data were extracted from six 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.

RESULTS: A total of 3,625 patients with localized deficient mismatch repair colorectal cancer 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, gender, and comorbidities. After matching, 556 patients were included and loss of MSH2/MSH6 was significantly associated with better overall survival (hazard ratio 0.60; 95% CI, 0.37-0.94); however, not disease-free survival (hazard ratio 0.84; 95% CI, 0.54-1.30).

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