Brief Article
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World J Gastroenterol. Aug 28, 2013; 19(32): 5286-5294
Published online Aug 28, 2013. doi: 10.3748/wjg.v19.i32.5286
Somatic molecular changes and histo-pathological features of colorectal cancer in Tunisia
Sana Aissi, Marie Pierre Buisine, Farid Zerimech, Nadia Kourda, Amel Moussa, Mohamed Manai, Nicole Porchet
Sana Aissi, Mohamed Manai, Laboratory of Biochemistry and Molecular Biology, Science University of Tunis, 2092 El Manar Tunis, Tunisia
Sana Aissi, Marie Pierre Buisine, Nicole Porchet, Centre de Recherche Jean-Pierre Aubert, INSERM U837, 59000 Lille, France
Marie Pierre Buisine, Farid Zerimech, Nicole Porchet, Laboratory of Biochemistry and Molecular Biology, CHRU de Lille, 59000 Lille, France
Marie Pierre Buisine, Nicole Porchet, Medicine University of H Warembourg, University of Lille Nord de France, 59045 Lille, France
Nadia Kourda, Anatomopathology Department, Charles Nicolle Hospital of Tunis, 1006 Tunis, Tunisia
Amel Moussa, Gastro-Enterology Department, Charles Nicolle Hospital of Tunis, 1006 Tunis, Tunisia
Author contributions: Aissi S performed and designed of the study, genetics consultation and samples collection, acquisition and interpretation of the familial data, sample database management, analysis and interpretation of the data, and co-writing of the paper; Buisine MP contributed to the conception, design, and supervision of the study, tumor samples selection, analysis and interpretation of the data, and co-writing of the paper; Zerimech F contributed to the statistical analyses and critical revision of the paper; Kourda N contributed to the pathological diagnosis, tumor samples selection; Moussa A contributed to the conception and design of the study, treatment and follow-up of the patients, and clinical data collection; Manai M contributed to the oversight of the work; Porchet N contributed to the critical revision of the paper.
Supported by In part by a grant from the Tunisian Government (to Aissi S)
Correspondence to: Sana Aissi, PhD, Centre de Recherche Jean-Pierre Aubert, INSERM U837, 1 place de Verdun, 59000 Lille cedex, France. sana.aissi@hotmail.com
Telephone: +33-3-20298850 Fax: +33-3-20538562
Received: March 18, 2013
Revised: May 14, 2013
Accepted: July 4, 2013
Published online: August 28, 2013
Processing time: 162 Days and 1.6 Hours
Abstract

AIM: 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).

CONCLUSION: These findings suggest that MUC5AC expression analysis may be useful in the screening of Tunisian patients with high risk of CRC.

Keywords: DNA mismatch repair; KRAS; TP53; Mucin 5AC

Core tip: This study reports, for the first time in Tunisia, the value of various histo-pathologic features and somatic molecular changes [BRAF, KRAS, CTNNB1, TP53, mismatch repair (MMR) expression, microsatellite instability (MSI), MLH1 promoter methylation] in distinguishing patients with hereditary non polyposis colorectal cancer. Our results revealed that MUC5AC expression was significantly associated with 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 colorectal cancer (63% vs 23%, P = 0.039). These findings suggest that mucin 5AC expression analysis may be useful in the screening of Tunisian patients with high risk of colorectal cancer.