Mismatch repair system deficiency is associated with chemoradiotherapy resistance in locally advanced rectal adenocarcinoma patients

J Surg Oncol. 2022 Mar;125(4):692-702. doi: 10.1002/jso.26771. Epub 2021 Dec 17.

Abstract

Background and objectives: Previous studies have concluded that colorectal cancer patients with deficient mismatch repair (dMMR) usually have a good prognosis. However, some studies have suggested that the prognosis of rectal cancer patients with dMMR appears to be worse. Our aim was to investigate chemoradiotherapy resistance in dMMR rectal tumors.

Methods: A retrospective study of 217 patients with locally advanced rectal adenocarcinoma treated with chemoradiotherapy and total mesorectal excision surgery was conducted using immunohistochemistry to determine MMR status and propensity score matching models to reduce potential confounders. Kaplan-Meier analysis, log-rank test, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups.

Results: The 3-year DFS rates were 77.1% and 56.7% in the pMMR and dMMR groups, respectively. The pMMR group had significantly better DFS than the dMMR group (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.10-3.91; p = 0.019). However, there was no significant difference in OS between the two groups (45.7 [interquartile range, IQR], 39.3-72.1] vs. 47.5 [IQR, 29.5-72.1]) (HR, 1.39; 95% CI, 0.70-2.77; p = 0.35). Neither OS nor DFS was significantly different between the neoadjuvant chemoradiotherapy and postoperative chemoradiotherapy groups.

Conclusion: Locally advanced dMMR rectal adenocarcinoma exhibits greater chemoradiotherapy resistance than pMMR.

Keywords: chemoradiotherapy; dMMR; locally advanced rectal cancer; therapy resistance.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / therapy
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Chemoradiotherapy / methods*
  • DNA Mismatch Repair
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Radiation Tolerance*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / therapy
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • DNA Repair Enzymes