Clinicopathologic characteristics of resectable colorectal cancer with mismatch repair protein defects in Chinese population: Retrospective case series and literature review

Medicine (Baltimore). 2020 Jun 12;99(24):e20554. doi: 10.1097/MD.0000000000020554.

Abstract

Colorectal cancer (CRC) represents a major malignancy globally, with microsatellite instability as its second top molecular mechanism of carcinogenesis. Immunohistochemical (IHC), whose sensitivity and specificity exceed 90%, is used routinely to detect 4 MMR proteins (MLH1, PMS2, MSH2, and MSH6) for screening mismatch repair system defects. We aimed to assess associations of clinicopathologic characteristics with MMR status in resectable CRC patients.Stage I-III CRC cases administered surgical resection in Zhejiang Cancer Hospital in 2013 to 2015 were retrospectively analyzed. MLH1, MSH2, MSH6, and PMS2 protein amounts were evaluated immunohistochemically. Clinicopathological information, including age, sex, tumor location, histological subclass, disease stage, regional lymph node (LN) metastasis, American Joint Committee on Cancer (AJCC) 8th edition stage, and survival data were retrospectively reviewed.A total of 133 CRC cases were assessed, including 74 (55.6%), 45 (33.8%), 55 (41.4%), and 77 (57.9%) not expressing MLH1, MSH2, MSH6, and PMS2, respectively. There were significant associations of MLH1, MSH2, MSH6, and PMS2 proteins with age and sex (P < .05). MLH1, MSH2, and MSH6 (but not PMS2) showed positive associations with primary tumor location (P < .05). Of the 133 patients, 70 and 63 cases were affected on the right and left sides, respectively; significant associations of primary site with age and sex were observed (P < .05). Regarding the MMR status, MLH1, MSH2, and MSH6 protein expression levels were positively associated with primary site (P < .05). Five-year overall survival (OS) rates were 84.2% and 79.2% in left-side and right-side cases, respectively; 5-year disease-free survival (DFS) rates were 74.0% and 69.8%, respectively. Survival had no differences between left- and right-side patients in terms of OS (P = .318) and DFS (P = .481).These data demonstrate that 4 major dMMR proteins are expressed differently in left- and right-side CRCs, and survival is comparable in right- and left-side resectable CRC cases with dMMR.

Publication types

  • Observational Study

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • China / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / metabolism
  • MutL Protein Homolog 1 / metabolism
  • MutS Homolog 2 Protein / metabolism
  • Retrospective Studies
  • Young Adult

Substances

  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes