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Abstract
Aims To map the colorectal carcinoma (CRC) diseases with significant Wnt signalling pathway activation for delineating their clinicopathological and molecular profiles.
Methods Mapping is based on hierarchical clustering analyses of a series of 283 CRCs. Data tabulated were histopathological patterns, immunophenotypic differentiation, RAS, RAF, CTNNB1 mutations and microsatellite instability status, tumour-infiltrating lymphocytes (TILs) and genetic setting. Beta-catenin expression in more than 10% of cell nuclei in the centre of tumour serves as a surrogate marker of significant activation of Wnt signalling pathway.
Results Nuclei beta-catenin expression was present in 95% of CRCs; 56% of them met the criteria of high level of nuclei beta-catenin expression (≥10%). Proportion of beta-catenin positive nuclei was significantly higher in younger patients, rectal and left-sided colonic carcinomas. CRCs with high level of nuclei beta-catenin expression were regrouped into three clusters: (1) microsatellite stability (MSS) CRCs with no constitutive MAPK pathway activation including 90% of low-grade adenocarcinoma, NOS, with intestinal differentiation without TILs; (2) RAS-mutated MSS CRCs including low-grade adenocarcinoma, NOS, with intestinal differentiation and mucinous adenocarcinoma without TILs; (3) MSI-H CRCs including both BRAF-mutated CRCs evolving from serrated pathway and CTNNB1-mutated CRCs associated with Lynch syndrome.
Conclusions MSS low-grade adenocarcinoma, NOS, with intestinal differentiation without TILs (‘crypt-like adenocarcinoma’) might be the morphological pending of canonical molecular subtype of CRC defined as displayed molecular epithelial differentiation and upregulation of WNT in consensus molecular classification of CRC.
- colorectal neoplasms
- immunohistochemistry
- biomarkers
- tumor
- cell differentiation
Data availability statement
All data relevant to the study are included in the article or uploaded as supplemental information.
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Data availability statement
All data relevant to the study are included in the article or uploaded as supplemental information.
Footnotes
Handling editor Runjan Chetty.
Contributors J-FM written and designed the study. FA, SM, SB and MD generated data. CV managed statistical study.
Funding This work was co-funded by the French Direction de l'Hospitalisation et de l'Organisation des Soins (DHOS) and INSERM (PROG/09/03).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note Tumorothéque du CHU de Nantes: Management of specimen collection
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