Epigenetics could explain some Moroccan population colorectal cancers peculiarities: microsatellite instability pathway exploration

Mohammed Sekal, Hassania Ameurtesse, Laila Chbani, Karim Ouldim, Sanae Bennis, Mohammed Abkari, Amal Boulouz, Dafr Allah Benajah, Basher Benjelloun, Abdelmalek Ousadden, Khalid Ait Taleb, Said Ait Laalim, Imane Toghrai, Khalid Mazaz, Samia Arifi, Nawfel Mellas, Karima El Rhazi, Taoufiq Harmouch, Sidi Adil Ibrahimi, Afaf Amarti Riffi

Colorectal Cancers (CRC) are one of the most common malignancies in the world. Their incidence in Morocco, between 2005 and 2007, was 5.6 for 100000 inhabitants, which is very low compared to what found in developed countries. In addition, CRCs show a high frequency of rectal localizations, and occurs in a younger population in Morocco compared to what found in developed countries. The purpose of this study is to confirm these CRC peculiarities in Morocco and try to explain them by exploring the microsatellite instability molecular pathway. This is a prospective observational study conducted since January 2010, including 385 patients admitted in Hassan II University Hospital of Fez. We collected clinical, radiological and pathological data. We investigated the expression of mismatch repair (MMR) proteins in 214 patients and BRAF gene mutations in 159 patients. Mean age was 55.08 +/- 15.16 years. 36.5 % of patients were less than 50 years old and 49.3 % of tumors were localized in the rectum. Loss of MMR protein expression was observed in 11.2 % of cases. It was independently associated with individual or family history of cancer belonging to Hereditary Non-Polyposis Colorectal Cancer (HNPCC) spectrum (p = 0.01) and proximal localization (p = 0.02). No BRAF mutation was detected in all cases. These results confirm the high occurrence of CRCs to young patients and the high frequency of rectal localizations in Moroccan population. They mostly show an absence of BRAF mutation, supposing a rarity of MLH1 promoter hypermethylation pathway, which may even partially explain the CRC peculiarities in our context. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5868184711716884.