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Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin-eosin-based morphologic parameters from the WHO classification

Title: Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin-eosin-based morphologic parameters from the WHO classification
Authors: Konukiewitz, Björn; Schmitt, Maxime; Silva, Miguel; Pohl, Junika; Lang, Corinna; Steiger, Katja; Halfter, Kathrin; Engel, Jutta; Schlitter, Anna Melissa; Boxberg, Melanie; Pfarr, Nicole; Wilhelm, Dirk; Foersch, Sebastian; Tschurtschenthaler, Markus; Weichert, Wilko; Jesinghaus, Moritz
Publisher Information: Springer Science and Business Media LLC
Publication Year: 2021
Collection: Christian-Albrechts-Universität zu Kiel: MACAU
Subject Terms: article; ScholarlyArticle; Published Version; ddc:610; Humans; Colorectal Neoplasms; Hematoxylin; Eosine Yellowish-(YS); Prognosis; World Health Organization; Female; Male; Microsatellite Instability; CDX2 Transcription Factor
Description: Background Immunohistochemical loss of CDX2 has been proposed as a biomarker of dismal survival in colorectal carcinoma (CRC), especially in UICC Stage II/III. However, it remains unclear, how CDX2 expression is related to central hematoxylin-eosin (HE)-based morphologic parameters defined by 2019 WHO classification and how its prognostic relevance is compared to these parameters. Methods We evaluated CDX2 expression in 1003 CRCs and explored its prognostic relevance compared to CRC subtypes, tumour budding and WHO grade in the overall cohort and in specific subgroups. Results CDX2-low/absent CRCs were enriched in specific morphologic subtypes, right-sided and microsatellite-instable (MSI-H) CRCs (P < 0.001) and showed worse survival characteristics in the overall cohort/UICC Stage II/III (e.g. DFS: P = 0.005) and in microsatellite stable and left-sided CRCs, but not in MSI-H or right-sided CRCs. Compared with CDX2, all HE-based markers showed a significantly better prognostic discrimination in all scenarios. In multivariate analyses including all morphologic parameters, CDX2 was not an independent prognostic factor. Conclusion CDX2 loss has some prognostic impact in univariate analyses, but its prognostic relevance is considerably lower compared to central HE-based morphologic parameters defined by the WHO classification and vanishes in multivariate analyses incorporating these factors.
Document Type: article in journal/newspaper
Language: English
Relation: British journal of cancer -- 0007-0920 -- 1532-1827
DOI: 10.1038/s41416-021-01553-0
Availability: https://doi.org/10.1038/s41416-021-01553-0; https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2025-01438-8; https://macau.uni-kiel.de/receive/macau_mods_00006984; https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00008474/s41416-021-01553-0.pdf
Rights: https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess
Accession Number: edsbas.A5DABA2D
Database: BASE