title: Selection of patients for hepatic surgery of colorectal cancer liver metastasis based on genomic aberrations.
abstract: BACKGROUND
  We investigated whether genomic aberrations in primary colorectal cancer (CRC) can identify patients who are at increased risk of developing additional hepatic recurrence after colorectal liver metastases (CLM) resection.
  
  
  METHODS
  Primary tumour DNA from 79 CLM resected patients was analysed for recurrent copy number changes (12x135k NimbleGen(™) aCGH). The cohort was divided into three groups: CLM patients with a recurrence-free survival after hepatic resection of at least 5 years (n = 21), patients who developed intra-hepatic recurrence (n = 32), and patients who developed extrahepatic recurrence (n = 26). By contrasting the primary tumour profiles of recurrence free and the extrahepatic recurrence CLM patients, a classifier, the extra-hepatic recurrence classifier (ERC1), predictive for subsequent extrahepatic-recurrence was developed.
  
  
  RESULTS
  The ERC1 had an accuracy of 70 % (95 % confidence interval (CI): 55-82 %, misclassification error 30 %, base error rate: 45 %). This analysis identified a region on Chromosome 12p13 as differentially aberrated between these two groups. The classifier was further optimized by contrasting the extrahepatic recurrence group with the combined group of intrahepatic and no recurrence group, resulting in an extrahepatic prognostic classifier (ERC2) able to classify patients with CLMs suitable for hepatic resection with 74 % accuracy (95 % CI: 62-83 %, misclassification error 26 %, base error rate: 32 %).
  
  
  CONCLUSIONS
  Patients with CLM who will develop extrahepatic recurrence may be identified with ERCs based on information in the primary tumour. Risk estimates for the occurrence of extrahepatic metastases may allow a reduction of hepatic resections of colorectal liver metastases for those who are unlikely to develop extrahepatic metastases.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, s.bruin@nki.nl.
authors.forename: Sjoerd C
authors.initials: SC
authors.lastname: Bruin
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: de Ronde
authors.forename: Bas
authors.initials: B
authors.lastname: Wiering
authors.forename: Linde M
authors.initials: LM
authors.lastname: Braaf
authors.forename: J H W
authors.initials: JH
authors.lastname: de Wilt
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Vincent
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: T J
authors.initials: TJ
authors.lastname: Ruers
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D023281:Genomics; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D011379:Prognosis
chemical_list: D004273:DNA, Neoplasm