title: Chromosome 20p11 gains are associated with liver-specific metastasis in patients with colorectal cancer.
abstract: OBJECTIVE
  Metastatic colorectal cancer (CRC) cells have a selective preference for certain target organs that cannot be explained by circulatory patterns alone. This study aimed to identify clinicopathological features and chromosomal aberrations of primary tumours associated with organ-specific CRC metastasis.
  
  
  METHODS
  Clinicopathological features were investigated in patients with CRC who had exclusively hepatic (n=182) versus exclusively extrahepatic (n=139) metastases. A total of 139 primary tumours of patients with hepatic (n=85) and extrahepatic metastases (n=54) were screened for chromosomal aberrations by microarray-based comparative genomic hybridisation, and the findings were validated in an independent set of 80 primary tumours. A publicly available database was used to correlate chromosomal aberrations with gene expression. Protein expression was evaluated by immunohistochemistry on tissue microarrays.
  
  
  RESULTS
  Patients with hepatic metastases were significantly more often male (71% vs 53% p=0.002), more often had abnormal lactate dehydrogenase activity (37% vs 14% p<0.0001), exhibited primary tumour localisation in the colon (52% vs 40% p=0.03) and had synchronous onset of metastases (70% vs 19% p<0.0001). Primary tumours of patients with hepatic metastases were more commonly T3 tumours (79% vs 63% p=0.006) and less commonly of mucinous histology (5% vs 16% p=0.02). Gain of 20p11 was more often observed in patients with hepatic metastases (p<0.05), which was confirmed in an independent dataset (p<0.05; false discovery rate <0.05). Twelve genes mapping at 20p11 were significantly overexpressed as a consequence of 20p11 copy number gain. C20orf3 showed the strongest correlation between RNA expression and DNA copy number. This was reflected in significantly higher protein expression in patients with hepatic metastases (59%; n=325) than in those with extrahepatic metastases (41%; n=256) (p=0.01).
  
  
  CONCLUSIONS
  C20orf3 mapping at 20p11 is associated with hepatic-specific metastasis in patients with CRC. This gene is a candidate biomarker for liver metastases and may be of clinical value in early-stage CRC.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Leonie J M
authors.initials: LJ
authors.lastname: Mekenkamp
authors.forename: Josien C
authors.initials: JC
authors.lastname: Haan
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.forename: M Elisa
authors.initials: ME
authors.lastname: Vink-Börger
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Israeli
authors.forename: Steven
authors.initials: S
authors.lastname: Teerenstra
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D058674:Chromosome Duplication; D002890:Chromosomes, Human, Pair 20; D015179:Colorectal Neoplasms / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D005819:Genetic Markers; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: C000601414:APMAP protein, human; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D008565:Membrane Proteins