title: Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer.
abstract: BACKGROUND
  We evaluated the association between a KRAS mutational status and various clinicopathologic features including the metastatic pattern in patients with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed.
  
  
  METHODS
  The KRAS mutational status in codons 12, 13, and 61 from formalin-fixed sections of both primary tumors and related metastases was determined by sequencing analysis. One hundred forty-three Korean patients with MRCRC with available tissues (resection or biopsy) from both primary tumors and related metastatic sites were consecutively enrolled.
  
  
  RESULTS
  The KRAS mutation rate was 52.4% (75/143) when considering both the primary and metastatic sites. When the relationship between the KRAS status and initial metastatic sites at the time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the initial metastatic site in patients with the KRAS mutation than in patients without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs. 70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025) were less frequent as the initial metastatic organ in patients with the KRAS mutation than in patients without the KRAS mutation. The discordance rate of KRAS mutational status between primary and paired metastatic sites other than the lung was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate was significantly higher in matched lung metastases [32.4% (12/37)] than in other matched metastatic organs (P = 0.005).
  
  
  CONCLUSIONS
  Organs initially involved by distant metastasis were different according to the KRAS mutational status in MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at metastatic sites other than the lung was generally high compared with primary tumor sites; however, lung metastasis had a high rate of KRAS discordance (32.4%).
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kwon
authors.forename: Jeong-Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Soo-Mee
authors.initials: SM
authors.lastname: Bang
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Keun-Wook
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D055815:Young Adult