title: Evaluation of microsatellite instability, MLH1 expression and hMLH1 promoter hypermethylation in colorectal carcinomas among Tunisians patients.
abstract: BACKGROUND
  About 10% to 15% of sporadic colorectal cancers demonstrate high level of microsatellite instability that is generally associated with aberrant methylation of hMLH1 promoter.
  
  
  OBJECTIVE
  To investigate the association between MSI status, hMLH1 protein expression and methylation status of the hMLH1 promoter in a cohort of Tunisian sporadic colorectal cancer.
  
  
  METHODS
  Expression of MLH1 and MSH2 was determined by immunohistochemistry and the MSI status was analysed by microfluid-based on-chip electrophoresis. Methylation of the hMLH1 gene promoter was determined by methylation-specific PCR.
  
  
  RESULTS
  Of the 150 colorectal cancers 57% were MSS, 28% were MSI-L and 15%were MSI-H. MSI-H tumors were more frequently right-sided, exhibited a stage III of TNM and tended more to be mucinous. The MSI status had no effect on overall patient survival. Most of the MSS/MSI-L 79% cancers were unmethylated at the hMLH1 promoter, while 26% MSI-H cancers were unmethylated. 84% of MSS and MSI-L expressed MLH1 and 52% of MSI-H expressed MLH1. Of the methylated MSI-H cases, 35% expressed MLH1 protein while 100% of the unmethylated MSI-H were positive for MLH1 staining. Of 11 MSI-H cancers with loss of MLH1 expression, all cases were also methylated while 50% MSI-H cancers with positive immunostaining for MLH1 were methylated at the hMLH1 promoter.
  
  
  CONCLUSIONS
  Our study showed that MSI-H phenotype was mucinous, right-side and exhibit stade III of TNM. The relative correlation of MLH1 expression and promotor hypermethylation of hMLH1 for the MSI status is similar to that reported for several study.
authors.affiliation: Department of Colorectal Cancer Research, URO3ES04 Science University, El Manar, Tunis, Tunisia.
authors.forename: Lilia
authors.initials: L
authors.lastname: Kria Ben Mahmoud
authors.forename: Amira
authors.initials: A
authors.lastname: Arfaoui
authors.forename: Mariem
authors.initials: M
authors.lastname: Khiari
authors.forename: Ines
authors.initials: I
authors.lastname: Chaar
authors.forename: Amine
authors.initials: A
authors.lastname: Lounis
authors.forename: Souraya
authors.initials: S
authors.lastname: Sammoud
authors.forename: Abdel Majid
authors.initials: AM
authors.lastname: Ben Hmida
authors.forename: Lasaad
authors.initials: L
authors.lastname: Gharbi
authors.forename: Sabeh Regaya
authors.initials: SR
authors.lastname: Mzabi
authors.forename: Saadia
authors.initials: S
authors.lastname: Bouraoui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D014416:Tunisia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1