title: The complex intratumoral heterogeneity of colon cancer highlighted by laser microdissection.
abstract: OBJECTIVE
  To evaluate the utility of laser microdissection in the comparison of phenotypes and genetic alterations between colon cancer and corresponding liver metastasis in the context of intratumoral heterogeneity.
  
  
  METHODS
  Immunohistochemistry was performed on a series of 11 patients surgically treated for colon adenocarcinoma with liver metastases, using antibodies directed against six mucins. Immunohistochemistry was completed by laser microdissection of tumor zones with particular phenotype, luminal zone and invasion front of colon tumors. Microdissected samples were compared on the basis of microsatellite instability and alterations of CTNNB1, KRAS, and TP53.
  
  
  RESULTS
  Our study demonstrated varying mucin expression within tumors, suggesting the existence of phenotypic intratumoral heterogeneity. A common immunohistochemical profile was observed in individual tumors between tumoral subpopulations and corresponding metastases. Nevertheless, the phenotypic characteristics were distinct from one patient to another. Laser microdissection underlined that phenotypic heterogeneity could rely on genotypic heterogeneity, and that some genetic alterations were common to microdissected samples from primary colon tumors and liver metastases.
  
  
  CONCLUSIONS
  We illustrated intratumoral heterogeneity of colon cancer using laser microdissection, in combination with immunohistochemical and genotypic tools. This intratumoral heterogeneity could represent a major issue in the search of prognostic biomarkers.
authors.affiliation: Department of Pathology, CHRU de Lille, Centre de Biologie Pathologie, Avenue Oscar Lambret, 59037 Lille Cedex, France. buob.david@gmail.com
authors.forename: David
authors.initials: D
authors.lastname: Buob
authors.forename: Harold
authors.initials: H
authors.lastname: Fauvel
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Truant
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.forename: Agnès
authors.initials: A
authors.lastname: Wacrenier
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary*; D000368:Aged; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D061346:Laser Capture Microdissection / Q000379:methods / Q000706:statistics & numerical data; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051176:beta Catenin / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins