title: The prognostic value of KRAS mutations in patients with colorectal cancer.
abstract: Our aim was to evaluate the KRAS genotypes of Japanese colorectal cancer (CRC) patients and to assess the effect of these genotypes on clinical outcome. A total of 99 patients with stage I-IV CRC who underwent resection were prospectively studied for KRAS mutations by direct sequencing. KRAS mutations were found in 37 (37.4%) of 99 patients. Of these, 11.1% were the KRAS p.G13D mutation and the remaining 26.2% were other KRAS mutations. The cumulative 5-year survival rates for patients with wild-type KRAS, KRAS 12 and KRAS p.G13D mutations were 81.4, 61.4 and 42.0%, respectively (P=0.0397). The KRAS genotype had no effect on stage IV patient prognosis without anti-epithelial growth factor receptor (EGFR) antibody therapy. However, in stage I-III patients significant or trends in prognostic factors for disease-free survival (DFS) were pathological T stage, lymphatic vessel involvement and KRAS p.G13D. Multivariate analysis identified T4 pathological stage (P=0.0076) and the KRAS p.G13D mutation (P=0.0499) as the most significant independent prognostic factors associated with DFS. In Japanese CRC patients KRAS p.G13D had prognostic impact on DFS in stage I-III disease, while the prognosis of stage IV patients without anti-EGFR antibody therapy was unaffected by KRAS status.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan. yasinoue@clin.medic.mie-u.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins