title: Somatic molecular changes and histo-pathological features of colorectal cancer in Tunisia.
abstract: OBJECTIVE
  To determine correlations between family history, clinical features and mutational status of genes involved in the progression of colorectal cancer (CRC).
  
  
  METHODS
  Histo-pathological features and molecular changes [KRAS, BRAF and CTNNB1 genes mutations, microsatellite instability (MSI) phenotype, expression of mismatch repair (MMR) and mucin (MUC) 5AC proteins, mutation and expression analysis of TP53, MLH1 promoter hypermethylation analysis] were examined in a series of 51 unselected Tunisian CRC patients, 10 of them had a proven or probable hereditary disease, on the track of new tumoral markers for CRC susceptibility in Tunisian patients.
  
  
  RESULTS
  As expected, MSI and MMR expression loss were associated to the presence of familial CRC (75% vs 9%, P < 0.001). However, no significant associations have been detected between personal or familial cancer history and KRAS (codons 12 and 13) or TP53 (exons 4-9) alterations. A significant inverse relationship has been observed between the presence of MSI and TP53 accumulation (10.0% vs 48.8%, P = 0.0335) in CRC tumors, suggesting different molecular pathways to CRC that in turn may reflect different environmental exposures. Interestingly, MUC5AC expression was significantly associated to the presence of MSI (46.7% vs 8.3%, P = 0.0039), MMR expression loss (46.7% vs 8.3%, P = 0.0039) and the presence of familial CRC (63% vs 23%, P = 0.039).
  
  
  CONCLUSIONS
  These findings suggest that MUC5AC expression analysis may be useful in the screening of Tunisian patients with high risk of CRC.
authors: Laboratory of Biochemistry and Molecular Biology, Science University of Tunis, 2092 El Manar Tunis, Tunisia. sana.aissi@hotmail.com
authors: Sana
authors: S
authors: Aissi
authors: Marie Pierre
authors: MP
authors: Buisine
authors: Farid
authors: F
authors: Zerimech
authors: Nadia
authors: N
authors: Kourda
authors: Amel
authors: A
authors: Moussa
authors: Mohamed
authors: M
authors: Manai
authors: Nicole
authors: N
authors: Porchet
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D055271:Mucin 5AC / Q000032:analysis; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D014416:Tunisia; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C117307:KRAS protein, human; C501486:MLH1 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: DNA mismatch repair; KRAS; Mucin 5AC; TP53
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