title: Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location.
abstract: Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. We sought to investigate the variable prognostic implication of KRAS mutation after hepatectomy for colorectal liver metastases (CRLM) according to the site of primary CRC.
  
  
  
  A total of 426 patients who underwent a curative-intent hepatic resection and whose KRAS status was available were identified. Clinicopathologic characteristics and long-term outcomes were stratified by KRAS status (wild type vs. mutant type) and primary tumor location (right-sided vs. left-sided). Cecum, right and transverse colon were defined as right-sided, whereas left colon and rectum were defined as left-sided.
  
  
  
  Among patients with a right-sided CRC, 5-year recurrence-free survival (RFS) and overall survival (OS) were not correlated with KRAS status (wild type: 30.8 and 47.2 % vs. mutant type: 38.5 and 49.1 %, respectively) (both P > 0.05). Specifically, mutant-type KRAS was not associated with either RFS or OS on multivariable analysis (hazard ratio [HR] 1.51, 95 % confidence interval [CI] 0.73-3.14, P = 0.23 and HR 1.03, 95 % CI 0.51-2.08, P = 0.95, respectively). In contrast, among patients who underwent resection of CRLM from a left-sided primary CRC, 5-year RFS and OS were worse among patients with mutant-type KRAS (wild type: 23.7 and 57.2 % vs. mutant type: 19.6 and 38.2 %, respectively) (both P < 0.05). On multivariable analysis, mutant-type KRAS remained independently associated with worse RFS and OS among patients with a left-sided primary CRC (HR 1.57, 95 % CI 1.01-2.44, P = 0.04 and HR 1.81, 95 % CI 1.11-2.96, P = 0.02, respectively).
  
  
  
  KRAS status has a variable prognostic impact after hepatic resection for CRLM depending on the site of the primary CRC. Future studies examining the impact of KRAS status on prognosis after hepatectomy should take into account the primary CRC tumor site.
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Yuhree
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Buettner
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Andreatos
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Faiz
authors.initials: F
authors.lastname: Gani
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Amini
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Gaya
authors.initials: G
authors.lastname: Spolverato
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. tpawlik1@jhmi.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000368:Aged; D002432:Cecum / Q000473:pathology; D044683:Colon, Descending / Q000473:pathology; D012809:Colon, Sigmoid / Q000473:pathology; D044684:Colon, Transverse / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)