title: A specific KRAS codon 13 mutation is an independent predictor for colorectal cancer metachronous distant metastases.
abstract: BACKGROUND
  In colorectal cancer, there are significant differences between synchronous and metachronous distant metastases. However in recent studies, synchronous and metachronous metastases were always lumped together, neglecting their clinical and molecular differences. The mechanism of the latency of metachronous metastases is still unclear. We conducted this study to reveal the relationship between EGFR pathways and metachronous metastases, and try to find efficient predictors.
  
  
  METHODS
  PCRs and pyrosequencing were used to detect KRAS, BRAF, PIK3CA and PTEN mutations in primary tumor tissues in a total of 281 patients from 2002 to 2008. Patients were identified into three groups: no-metastases group, synchronous-metastases group and metachronous-metastases group. Clinical and survival data were collected from a prospective database.
  
  
  RESULTS
  KRAS codon 13 mutation was an independent predictor only for metachronous distant metastases (OR = 11.857, P < 0.001), but not for synchronous metastases. Male gender (OR = 2.233, P = 0.024), primary tumor located at rectum (OR = 0.404, P = 0.041), and primary pN2 stage (OR = 3.361, P = 0.01) were also independent predictors for metachronous distant metastases. Different SNPs in KRAS worked significantly different in determining synchronous or metachronous metastases. BRAF mutation (Univariate, OR = 11.5, P = 0.039) and > 200 ng/ml preoperative CEA (Univariate, OR = 41, P = 0.011) potentially predicted metastases within 6 months after primary tumor resection. After metachronous metastases, radical resection (HR = 0.280, P = 0.002) was the most important protective factor for long-term survival.
  
  
  CONCLUSIONS
  There were significant clinical and molecular differences between synchronous and metachronous metastases. As an independent predictor, KRAS codon 13 mutation might be the key to explain the mechanism of colorectal cancer metachronous distant metastases. Together with clinical characteristics, it could aid in the early detection of metachronous metastases.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Internal Medicine/Oncology, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Xu
keywords: Colorectal cancer; KRAS mutation; metachronous metastases; predictor