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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.

Document type:
Journal Article
Author(s):
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
Abstract:
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.
Journal title abbreviation:
Br J Cancer
Year:
2021
Journal volume:
125
Journal issue:
12
Pages contribution:
1632-1646
Fulltext / DOI:
doi:10.1038/s41416-021-01553-0
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/34616012
Print-ISSN:
0007-0920
TUM Institution:
Institut für Allgemeine Pathologie und Pathologische Anatomie; Klinik und Poliklinik für Chirurgie; Lehrstuhl für Experimentelle Tumortherapie (Prof. Saur)
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