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The Complex Intratumoral Heterogeneity of Colon Cancer Highlighted by Laser Microdissection

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Abstract

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.

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Acknowledgments

The authors thank Ms A. Ketele (INSERM U837), Mrs V. Dumetz, Mrs V. Vervaeck, Ms S. Gosselin, Mr F. Romelard, Mr M. Samyn (Pathology Department), Mrs R.M. Siminski and Mrs M.H. Gevaert (Histology Department) for their technical assistance. The authors acknowledge Drs I. Carlstedt, D. Swallow, and S.K. Batra for providing antibodies.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Pathology, CHRU de Lille, Centre de Biologie Pathologie, Avenue Oscar Lambret, 59037, Lille Cedex, France

    David Buob, Agnès Wacrenier, Marie-Christine Copin & Emmanuelle Leteurtre

  2. Inserm, U837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis”, Institut de Médecine Prédictive et Recherche Thérapeutique, Jean-Pierre Aubert Research Centre, Bâtiment Gérard Biserte Place de Verdun, 59045, Lille, France

    David Buob, Marie-Pierre Buisine, Stéphanie Truant, Christophe Mariette, Nicole Porchet, Marie-Christine Copin & Emmanuelle Leteurtre

  3. Université Lille Nord de France, 59000, Lille, France

    David Buob, Marie-Pierre Buisine, Christophe Mariette, Nicole Porchet, Marie-Christine Copin & Emmanuelle Leteurtre

  4. Cell Imagery Department, IMPRT-IFR114, Faculté de Médecine, 1, Place de Verdun, 59045, Lille Cedex, France

    Harold Fauvel

  5. Department of Biochemistry and Molecular Biology, CHRU de Lille, Centre de Biologie Pathologie, Avenue Oscar Lambret, 59037, Lille Cedex, France

    Marie-Pierre Buisine & Nicole Porchet

  6. Department of Digestive Surgery and Transplantation, CHRU de Lille, Place de Verdun, 59037, Lille Cedex, France

    Stéphanie Truant

  7. Department of Digestive and Oncological Surgery, CHRU de Lille, Place de Verdun, 59037, Lille Cedex, France

    Christophe Mariette

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  1. David Buob
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  2. Harold Fauvel
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  3. Marie-Pierre Buisine
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  7. Agnès Wacrenier
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  9. Emmanuelle Leteurtre
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Correspondence to David Buob.

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Buob, D., Fauvel, H., Buisine, MP. et al. The Complex Intratumoral Heterogeneity of Colon Cancer Highlighted by Laser Microdissection. Dig Dis Sci 57, 1271–1280 (2012). https://doi.org/10.1007/s10620-011-2023-1

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  • DOI: https://doi.org/10.1007/s10620-011-2023-1

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