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
- 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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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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