The complex intratumoral heterogeneity of colon cancer highlighted by laser microdissection

Dig Dis Sci. 2012 May;57(5):1271-80. doi: 10.1007/s10620-011-2023-1. Epub 2011 Dec 25.


Aims: 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.

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / secondary*
  • Aged
  • Colon / pathology
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / pathology
  • Female
  • Genetic Heterogeneity
  • Genotyping Techniques / methods
  • Humans
  • Immunohistochemistry / methods
  • Laser Capture Microdissection* / methods
  • Laser Capture Microdissection* / statistics & numerical data
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / secondary
  • Male
  • Microsatellite Instability
  • Microsatellite Repeats
  • Middle Aged
  • Phenotype
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Tumor Suppressor Protein p53 / genetics
  • beta Catenin / genetics*
  • ras Proteins / genetics*


  • CTNNB1 protein, human
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins