title: Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening.
abstract: BACKGROUND
  Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.
  
  
  METHODS
  A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.
  
  
  RESULTS
  Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.
  
  
  CONCLUSIONS
  Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.
authors.affiliation: Department of Paediatric, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia E-mail : wfaiziah@usm.my.
authors.forename: Wan Khairunnisa
authors.initials: WK
authors.lastname: Wan Juhari
authors.forename: Wan Faiziah
authors.initials: WF
authors.lastname: Wan Abdul Rahman
authors.forename: Ahmad Shanwani
authors.initials: AS
authors.lastname: Mohd Sidek
authors.forename: Muhammad Radzi
authors.initials: MR
authors.lastname: Abu Hassan
authors.forename: Khairul Bariah
authors.initials: KB
authors.lastname: Ahmad Amin Noordin
authors.forename: Andee Dzulkarnaen
authors.initials: AD
authors.lastname: Zakaria
authors.forename: Finlay
authors.initials: F
authors.lastname: Macrae
authors.forename: Bin Alwi
authors.initials: BA
authors.lastname: Zilfalil
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000378:metabolism* / Q000473:pathology*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D010375:Pedigree; D011379:Prognosis; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; 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