title: Analysis of KRAS mutations in cases of metastatic colorectal cancer at a single institution in Tochigi, Japan.
abstract: OBJECTIVE
  Colorectal cancer patients bearing wild-type KRAS benefit from anti-epidermal growth factor receptor (EGFR) antibody treatment. Since clinical studies showed the efficacy of anti-EGFR antibody treatment for metastatic colorectal cancer (mCRC), we analyzed KRAS mutations in mCRC to gain insight into the association between these mutations and clinicopathological characteristics.
  
  
  METHODS
  KRAS mutations were analyzed in 109 tissue samples of mCRC using amplification refractory mutation system-Scorpion (ARMS/S) assay (68 samples) and direct sequencing (41 samples).
  
  
  RESULTS
  In the ARMS/S assay, 36.5 and 7.4% of mCRCs harbored mutations at codons 12 and 13, respectively. In direct sequencing, corresponding values were 24.4 and 19.5%. Overall, 37.6% (codon 12/13, 25.7/11.9%) of mCRCs harbored KRAS mutations. No significant differences were found between KRAS mutations and clinicopathological variables. Among mCRC patients <65 years of age, the incidence of KRAS mutations at codon 13 was significantly higher in female than male patients (p = 0.035).
  
  
  CONCLUSIONS
  The incidence of KRAS mutations in mCRC was similar to that of non-mCRC as previously reported. KRAS codon 13 mutations might be associated with younger female patients with mCRC, but further investigation is necessary to clarify the association between this type of mutation and metastatic potential in female CRC patients.
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Saito
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tomita
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Johji
authors.initials: J
authors.lastname: Imura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fujimori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins