title: Mismatch repair deficiency in colorectal cancer patients in a low-incidence area.
abstract: BACKGROUND
  In a previous study we identified 206 patients with colorectal adenocarcinoma in the Northern Cape province of South Africa, diagnosed between January 2002 and February 2009. The age-standardised incidence was 4.2/100 000 per year world standard population. This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%.
  
  
  OBJECTIVE
  The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the Northern Cape.
  
  
  METHODS
  Formalin-fixed paraffin wax-embedded tissue blocks from 87 colorectal adenocarcinomas identified in the previous study were retrieved. Standard immunohistochemical staining methods were used to detect the expression of hMLH1 and hMSH2 (i.e. products of the hMLH1 and hMSH2 genes) in the tumours using heat-induced antigen retrieval and diaminobenzidene as a chromogen. Results. In 8 blocks there was insufficient tumour tissue and in 1 case the immunohistochemical staining failed, probably owing to poor fixation, leaving 78 cases for analysis. In 11 cases hMLH1 was deficient and in 6 cases hMSH2 was deficient. Overall, 21.8% of cancers were deficient for hMLH1 or hMSH2.
  
  
  CONCLUSIONS
  Presuming that 80% of all hMLH1 deficiencies are due to hypermethylation of the gene, we found 10.5% of colorectal cancers in an area with a low incidence of colorectal cancer to be deficient in the product of the mismatch repair gene/s. This is approximately three times the reported rate in high-incidence areas.
authors.affiliation: Department of Surgery, University of Cape Town, Cape Town, South Africa. floorvergouwe@gmail.com
authors.forename: F
authors.initials: F
authors.lastname: Vergouwe
authors.forename: A
authors.initials: A
authors.lastname: Boutall
authors.forename: D
authors.initials: D
authors.lastname: Stupart
authors.forename: U
authors.initials: U
authors.lastname: Algar
authors.forename: D
authors.initials: D
authors.lastname: Govender
authors.forename: G D
authors.initials: GD
authors.lastname: van der Linde
authors.forename: A
authors.initials: A
authors.lastname: Mall
authors.forename: R
authors.initials: R
authors.lastname: Ramesar
authors.forename: P A
authors.initials: PA
authors.lastname: Goldberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C088996:PMS1 protein, human; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D045643:DNA Repair Enzymes