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

被引:20
作者
El Agy, Fatima [1 ,2 ]
el Bardai, Sanae [2 ]
El Otmani, Ihsane [1 ,2 ,3 ]
Benbrahim, Zineb [4 ]
Karim, Ibn Majdoub Hassani [5 ]
Mazaz, Khalid [5 ]
Benjelloun, El Bachir [5 ]
Ousadden, Abdelmalek [5 ]
El Abkari, Mohammed [6 ]
Ibrahimi, Sidi Adil [5 ]
Chbani, Laila [1 ,2 ]
机构
[1] Sidi Mohamed Ben Abdellah Univ, Fac Med & Pharm, Lab Biomed & Translat Res, Fes, Morocco
[2] Sidi Mohamed Ben Abdellah Univ, Univ Hosp Hassan II, Lab Anat Pathol & Mol Pathol, Fes, Morocco
[3] Sidi Mohamed Ben Abdellah Univ, Univ Hosp Hassan II, Unit Med Genet & Oncogenet, Fes, Morocco
[4] Sidi Mohamed Ben Abdellah Univ, Univ Hosp Hassan II, Dept Oncol, Fes, Morocco
[5] Sidi Mohamed Ben Abdellah Univ, Univ Hosp Hassan II, Dept Gen Surg, Fes, Morocco
[6] Sidi Mohamed Ben Abdellah Univ, Univ Hosp Hassan II, Dept Gastroenterol, Fes, Morocco
关键词
D O I
10.1371/journal.pone.0248522
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:21
相关论文
共 51 条
[1]   K-ras mutations and prognosis in large-bowel carcinomas [J].
Andersen, SN ;
Lovig, T ;
Breivik, J ;
Lund, E ;
Gaudernack, G ;
Meling, GI ;
Rognum, TO .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1997, 32 (01) :62-69
[2]   Kirsten ras mutations in patients with colorectal cancer:: the 'RASCAL II' study [J].
Andreyev, HJN ;
Norman, AR ;
Cunningham, D ;
Oates, J ;
Dix, BR ;
Iacopetta, BJ ;
Young, J ;
Walsh, T ;
Ward, R ;
Hawkins, N ;
Beranek, M ;
Jandik, P ;
Benamouzig, R ;
Jullian, E ;
Laurent-Puig, P ;
Olschwang, S ;
Muller, O ;
Hoffmann, I ;
Rabes, HM ;
Zietz, C ;
Troungos, C ;
Valavanis, C ;
Yuen, ST ;
Ho, JWC ;
Croke, CT ;
O'Donoghue, DP ;
Giaretti, W ;
Rapallo, A ;
Russo, A ;
Bazan, V ;
Tanaka, M ;
Omura, K ;
Azuma, T ;
Ohkusa, T ;
Fujimori, T ;
Ono, Y ;
Pauly, M ;
Faber, C ;
Glaesener, R ;
de Goeij, AFPM ;
Arends, JW ;
Andersen, SN ;
Lövig, T ;
Breivik, J ;
Gaudernack, G ;
Clausen, OPF ;
De Angelis, P ;
Meling, GI ;
Rognum, TO ;
Smith, R .
BRITISH JOURNAL OF CANCER, 2001, 85 (05) :692-696
[3]  
Baltruskeviien E., 2016, SIGNIFICANCE KRAS NR, V23, P24, DOI [10.6001/actamedica.v23i1.3267, DOI 10.6001/ACTAMEDICA.V23I1.3267]
[4]  
Barbie DA., 2010, PROCESSING A PROGRAM, V462, P108
[5]  
Barras D., 2016, BRAF V600E MUTANT CO, DOI [10.1158/1078-0432.CCR-16-0140, DOI 10.1158/1078-0432.CCR-16-0140]
[6]   Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset [J].
Blons, H. ;
Emile, J. F. ;
Le Malicot, K. ;
Julie, C. ;
Zaanan, A. ;
Tabernero, J. ;
Mini, E. ;
Folprecht, G. ;
Van Laethem, J. L. ;
Thaler, J. ;
Bridgewater, J. ;
Norgard-Petersen, L. ;
Van Cutsem, E. ;
Lepage, C. ;
Zawadi, M. A. ;
Salazar, R. ;
Laurent-Puig, P. ;
Taieb, J. .
ANNALS OF ONCOLOGY, 2014, 25 (12) :2378-2385
[7]   Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention [J].
Colussi, Dora ;
Brandi, Giovanni ;
Bazzoli, Franco ;
Ricciardiello, Luigi .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (08) :16365-16385
[8]   The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma [J].
Conlin, A ;
Smith, G ;
Carey, FA ;
Wolf, CR ;
Steele, RJC .
GUT, 2005, 54 (09) :1283-1286
[9]   Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis [J].
De Roock, Wendy ;
Claes, Bart ;
Bernasconi, David ;
De Schutter, Jef ;
Biesmans, Bart ;
Fountzilas, George ;
Kalogeras, Konstantine T. ;
Kotoula, Vassiliki ;
Papamichael, Demetris ;
Laurent-Puig, Pierre ;
Penault-Llorca, Frederique ;
Rougier, Philippe ;
Vincenzi, Bruno ;
Santini, Daniele ;
Tonini, Giuseppe ;
Cappuzzo, Federico ;
Frattini, Milo ;
Molinari, Francesca ;
Saletti, Piercarlo ;
De Dosso, Sara ;
Martini, Miriam ;
Bardelli, Alberto ;
Siena, Salvatore ;
Sartore-Bianchi, Andrea ;
Tabernero, Josep ;
Macarulla, Teresa ;
Di Fiore, Frederic ;
Gangloff, Alice Oden ;
Ciardiello, Fortunato ;
Pfeiffer, Per ;
Qvortrup, Camilla ;
Hansen, Tine Plato ;
Van Cutsem, Eric ;
Piessevaux, Hubert ;
Lambrechts, Diether ;
Delorenzi, Mauro ;
Tejpar, Sabine .
LANCET ONCOLOGY, 2010, 11 (08) :753-762
[10]   Panitumumab-FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer [J].
Douillard, Jean-Yves ;
Oliner, Kelly S. ;
Siena, Salvatore ;
Tabernero, Josep ;
Burkes, Ronald ;
Barugel, Mario ;
Humblet, Yves ;
Bodoky, Gyorgy ;
Cunningham, David ;
Jassem, Jacek ;
Rivera, Fernando ;
Kocakova, Ilona ;
Ruff, Paul ;
Blasinska-Morawiec, Maria ;
Smakal, Martin ;
Canon, Jean Luc ;
Rother, Mark ;
Williams, Richard ;
Rong, Alan ;
Wiezorek, Jeffrey ;
Sidhu, Roger ;
Patterson, Scott D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (11) :1023-1034