title: Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment.
abstract: BACKGROUND
  Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated with a conspicuous local immune infiltrate; however, its relationship with systemic inflammatory responses remains to be determined. The present study aims to examine the relationships and prognostic value of assessment of the local and systemic environment in the context of MMR status in patients with CRC.
  
  
  METHODS
  The relationship between MMR status, determined using immunohistochemistry, and the local inflammatory cell infiltrate, differential white cell count, neutrophil : platelet score (NPS), neutrophil : lymphocyte ratio and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I-III CRC.
  
  
  RESULTS
  Thirty-five patients (15%) had dMMR CRC. Mismatch repair deficiency was associated with a higher density of CD3(+), CD8(+) and CD45R0(+) T lymphocytes within the cancer cell nests and an elevated mGPS (mGPS2: 23% vs 9%, P=0.007) and NPS (NPS2: 19% vs 3%, P=0.001). CD3(+) density (P<0.001), mGPS (P=0.01) and NPS (P=0.042) were associated with survival independent of MMR status (P=0.367) and stratified 5-year survival of patients with MMR-competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively.
  
  
  CONCLUSIONS
  Mismatch repair deficiency was associated with local and systemic environments, and in comparison with their assessment, dMMR had relatively poor prognostic value in patients with primary operable CRC. In addition to MMR status, local and systemic inflammatory responses should be assessed in these patients.
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.|Unit of Experimental Therapeutics, Institute of Cancer Science, University of Glasgow, Garscube Estate, Glasgow, UK.
authors: James H
authors: JH
authors: Park
authors: Institute of Cancer and Genetics, University of Cardiff, Cardiff, UK.
authors: Arfon G
authors: AG
authors: Powell
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
authors: Campbell S D
authors: CS
authors: Roxburgh
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
authors: Paul G
authors: PG
authors: Horgan
authors: Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
authors: Donald C
authors: DC
authors: McMillan
authors: Unit of Experimental Therapeutics, Institute of Cancer Science, University of Glasgow, Garscube Estate, Glasgow, UK.
authors: Joanne
authors: J
authors: Edwards
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology; D053843:DNA Mismatch Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007958:Leukocyte Count; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment / Q000235:genetics* / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes