title: Immunochemistry screening for Lynch syndrome in colorectal adenocarcinoma using an initial two antibody panel can replace a four antibody panel.
abstract: OBJECTIVE
  The current practice in immunochemistry staining for Lynch syndrome (LS) is to use a four-antibody panel, (MLH1, MSH2, MSH6, PMS2) to screen for the four Mismatch Repair (MMR) gene expressions involved. We hypothesised that testing two antibodies (MSH6 and PMS2), followed by the other two only when there is loss of expression of the first two antibodies, would be equally effective as a four antibody panel in detecting LS. This hypothesis is based on the biochemical binding properties of the MMR proteins.
  
  
  METHODS
  We tested this hypothesis on a patient cohort consisting of all cases of colorectal cancer that were stained for MMR gene expression at Auckland City Hospital (Auckland, New Zealand) from the years 2000 to 2010 (inclusive), providing a series of 410 cases for this study. Exclusions were made based on heterogeneous staining pattern and unsatisfactory staining results on MSH6 and PMS2, which left n=400 included in the study.
  
  
  RESULTS
  The MMR gene protein stains were regarded as demonstrating loss of expression (LOE) when there was no uptake in the nucleus of the tumour cells, with a positive internal control. The results from our analysis supported our hypothesis. Seventy-four cases showed LOE of MSH6 or PMS2. One of them showed LOE of all four MMR proteins. For the remaining 326 cases, there was no LOE of all four MMR proteins.
  
  
  CONCLUSIONS
  Our study gives further evidence that an initial two-antibody panel consisting of PMS2 and MSH6 would be as effective as a four-antibody panel in detecting DNA MMR gene protein LOE. This study has implications for significant cost cutting and improved efficiency in detection of DNA MMR gene protein LOE in LS.
authors.affiliation: LabPlus, Auckland City Hospital, Private Bag 92024, Auckland Mail Centre, Auckland 1142, New Zealand. kaiyinc@adhb.govt.nz.
authors.forename: Toni
authors.initials: T
authors.lastname: O'Regan
authors.forename: Kai
authors.initials: K
authors.lastname: Chau
authors.forename: Michael
authors.initials: M
authors.lastname: Tatton
authors.forename: Tania
authors.initials: T
authors.lastname: Smith
authors.forename: Susan
authors.initials: S
authors.lastname: Parry
authors.forename: Ian
authors.initials: I
authors.lastname: Bissett
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D045643:DNA Repair Enzymes / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D055815:Young Adult
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; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes