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Hierarchical clustering identifies a subgroup of colonic adenocarcinomas expressing crypt-like differentiation markers, associated with MSS status and better prognosis

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Abstract

The aim of this study was to identify in the group of colonic adenocarcinomas, not otherwise specified (NOS), subgroups of oncogenetic and prognostic significance based on the expression of immunohistochemical markers of epithelial cell differentiation of the gastrointestinal tract. Hierarchical clustering analysis of 122 adenocarcinomas (NOS) identified four clusters based on how closely their profile of immunohistochemical expression of differentiation markers was related: (i) a major cluster of 83 adenocarcinomas (68 %) called crypt-like carcinoma (CLA) with a immunohistochemically expressing colonic crypt differentiation markers (cytokeratin 20+, CDX2+, MUC2+ or MUC2−) and (ii) three minor clusters, characterized by the loss of colonic crypt differentiation markers and/or the acquisition of expression of markers of metaplastic foveolar gastric differentiation (MUC5AC+) and/or aberrant cytokeratin 7 expression. CLAs were invariably MSS (χ 2 test: p < 0.0001). The sole parameters associated with worse overall survival of the 122 patients with adenocarcinoma (NOS) were pT stage, pN+ stage, and advanced clinical stage. Interestingly, CLA lineage of differentiation was an independent prognostic parameter for better overall survival among the 40 patients with an adenocarcinoma (NOS) stage III. In conclusion, hierarchical clustering led to the identification of a main cluster of adenocarcinoma (NOS) with crypt-like differentiation, associated with MSS status and better prognosis. Its value as a biomarker of response to conventional chemotherapeutic agents deserves to be examined in randomized therapy trials.

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Acknowledgments

This study is funded by a grant from “Projet Hospitalier de Recherche Clinique” PHRC BRD 07 from the French “Direction de l’Hospitalisation et l’Organisation des Soins” (DHOS). The authors thank the “Photologie” Department for their help.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Centre Hospitalier Universitaire, Nantes, France

    Laure Droy-Dupré, Céline Bossard, Christian L. Laboisse & Jean-François Mosnier

  2. Biostatistics Department, Centre Hospitalier Universitaire, Nantes, France

    Christelle Volteau

  3. Department of Genetics, Centre Hospitalier Universitaire, Nantes, France

    Stéphane Bezieau

  4. Service d’Anatomie Pathologique, Hôtel Dieu, 1 place Ricordeau, 44093, Nantes, France

    Jean-François Mosnier

Authors
  1. Laure Droy-Dupré
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  2. Céline Bossard
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  4. Stéphane Bezieau
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  5. Christian L. Laboisse
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Correspondence to Jean-François Mosnier.

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Droy-Dupré, L., Bossard, C., Volteau, C. et al. Hierarchical clustering identifies a subgroup of colonic adenocarcinomas expressing crypt-like differentiation markers, associated with MSS status and better prognosis. Virchows Arch 466, 383–391 (2015). https://doi.org/10.1007/s00428-015-1724-9

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  • DOI: https://doi.org/10.1007/s00428-015-1724-9

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