title: A Validated Prognostic Multigene Expression Assay for Overall Survival in Resected Colorectal Cancer Liver Metastases.
abstract: Risk stratification after surgery for colorectal cancer liver metastases (CRLM) is achieved using clinicopathologic variables, however, is of limited accuracy. We sought to derive and externally validate a multigene expression assay prognostic of overall survival (OS) that is superior to clinicopathologic variables in patients with surgically resected CRLM.
  
  
  
  We measured mRNA expression in prospectively collected frozen tumor from 96 patients with surgically resected CRLM at Memorial Sloan Kettering Cancer Center (MSKCC, New York, NY). We retrospectively generated a 20-gene molecular risk score (MRS) and compared its prognostic utility for OS and recurrence-free survival (RFS) with three common clinical risk scores (CRS). We then tested the prognostic ability of the MRS in an external validation cohort (European) of 119 patients with surgically resected CRLM at the University Medical Center Utrecht (Utrecht, the Netherlands) and Paul Brousse Hospital (Villejuif, France).
  
  
  
  For OS in the MSKCC cohort, MRS was the strongest independent prognosticator (HR, 3.7-4.9; P < 0.001) followed by adjuvant chemotherapy (HR, 0.3; P ≤ 0.001). For OS in the European cohort, MRS was the only independent prognosticator (HR, 3.5; P = 0.007). For RFS, MRS was also independently prognostic in the MSKCC cohort (HR, 2.4-2.6; P ≤ 0.001) and the European cohort (HR, 1.6-2.5; P ≤ 0.05).
  
  
  
  Compared with CRSs, the MRS is more accurate, broadly applicable, and an independent prognostic biomarker of OS in resected CRLM. This MRS is the first externally validated prognostic multigene expression assay after metastasectomy for CRLM and warrants prospective validation. Clin Cancer Res; 22(10); 2575-82. ©2016 AACR.
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Balachandran
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Arshi
authors.initials: A
authors.lastname: Arora
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Surgery, Michigan State University, East Lansing, Michigan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Université de Montréal, and Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Turcotte
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.affiliation: Genomics Core Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Department of Surgery, University Medical Center, Utrecht, The Netherlands.
authors.forename: Nikol
authors.initials: N
authors.lastname: Snoeren
authors.affiliation: Molecular Cancer Research, University Medical Center, Utrecht, The Netherlands.
authors.forename: Sander R
authors.initials: SR
authors.lastname: van Hooff
authors.affiliation: Department of Surgery, University Medical Center, Utrecht, The Netherlands.
authors.forename: Inne H M Borel
authors.initials: IH
authors.lastname: Rinkes
authors.affiliation: Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France.
authors.forename: René
authors.initials: R
authors.lastname: Adam
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. dangelim@mskcc.org.
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger