title: Hierarchical clustering identifies a subgroup of colonic adenocarcinomas expressing crypt-like differentiation markers, associated with MSS status and better prognosis.
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.
authors: Department of Pathology, Centre Hospitalier Universitaire, Nantes, France.
authors: Laure
authors: L
authors: Droy-Dupré
authors: Céline
authors: C
authors: Bossard
authors: Christelle
authors: C
authors: Volteau
authors: Stéphane
authors: S
authors: Bezieau
authors: Christian L
authors: CL
authors: Laboisse
authors: Jean-François
authors: JF
authors: Mosnier
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071616:CDX2 Transcription Factor; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053554:Keratin-20 / Q000032:analysis / Q000096:biosynthesis; D053552:Keratin-7 / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D055271:Mucin 5AC / Q000032:analysis / Q000096:biosynthesis; D055262:Mucin-2 / Q000032:analysis / Q000096:biosynthesis; D011379:Prognosis; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D053554:Keratin-20; D053552:Keratin-7; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2