Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report.

Autor:	El Agy F; Faculty of Medicine and Pharmacy, Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University, Fez, Morocco.; Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., El Bardai S; Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., El Otmani I; Faculty of Medicine and Pharmacy, Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University, Fez, Morocco.; Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.; Unit of Medical Genetics and Oncogenetics, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Benbrahim Z; Department of Oncology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Karim MH; Department of General Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Mazaz K; Department of General Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Benjelloun EB; Department of General Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Ousadden A; Department of General Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., El Abkari M; Department of Gastroenterology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Ibrahimi SA; Department of General Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco., Chbani L; Faculty of Medicine and Pharmacy, Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University, Fez, Morocco.; Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2021 Mar 30; Vol. 16 (3), pp. e0248522. Date of Electronic Publication: 2021 Mar 30 (Print Publication: 2021).
DOI:	10.1371/journal.pone.0248522
Abstrakt:	This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population. Competing Interests: The authors have declared that no competing interests exist.
Databáze:	MEDLINE
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