title: Clinicopathological characteristics and prognostic impact of colorectal cancers with NRAS mutations.
abstract: At present, molecular markers of colorectal cancer (CRC), including KRAS, NRAS and BRAF mutations, and the microsatellite status are evaluated for the development of personalized treatments. However, clinicopathological and molecular characteristics and the prognostic role of NRAS mutations remain unclear. In the present study, a total of 1,304 consecutive stage 0-IV CRC tumor samples were analyzed for KRAS (exon 2, 3 and 4), NRAS (exon 2 and 3) and BRAF (exon 15) mutations. Multivariate analysis was performed to assess the prognostic impact of NRAS mutations. KRAS, NRAS and BRAF mutations were identified in 553 (42.4%), 35 (2.7%), and 59 (4.5%) of 1,304 CRC cases, respectively. Tumors with NRAS mutations were more frequently located in the distal colorectum compared with those with KRAS or BRAF mutations. Multivariate analysis indicated that KRAS and BRAF mutations were found to be associated with poor prognosis [hazard ratio (HR)=1.44, 95% confidence interval (CI), 1.18-1.76 and HR=2.09; 95% CI, 1.33-3.28, respectively], whereas NRAS mutations were associated with a trend toward favorable prognosis (HR=0.53; 95% CI, 0.27-1.03). Characteristics and prognosis of CRC with NRAS mutations are different from those with KRAS or BRAF mutations.
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ogura
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kakuta
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yatsuoka
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Division of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Akagi
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D053842:Microsatellite Instability; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins