title: Colorectal cancers mimic structural organization of normal colonic crypts.
abstract: Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes.
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany; Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Laura
authors.initials: L
authors.lastname: Cernat
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Blaj
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany; Experimentelle und molekulare Pathologie, Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Jackstadt
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Brandl
authors.affiliation: Tumorregister München (TRM), Klinikum der Universität, München, Germany; Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany; Experimentelle und molekulare Pathologie, Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany; Deutsches Konsortium für translationale Krebsforschung (DKTK), Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Hermeking
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany; Deutsches Konsortium für translationale Krebsforschung (DKTK), Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany; Deutsches Konsortium für translationale Krebsforschung (DKTK), Heidelberg, Germany; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: Pathologisches Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Horst
mesh_terms: D000368:Aged; D000818:Animals; D018938:Caco-2 Cells; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000166:cytology* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D010641:Phenotype; D016019:Survival Analysis
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