Logo image
Back
The role of APC in WNT pathway activation in serrated neoplasi
Journal article   Peer reviewed

The role of APC in WNT pathway activation in serrated neoplasi

Jennifer Borowsky, Troy Dumenil, Mark Bettington, Sally-Anne Pearson, Catherine Bond, Lochlan Fennell, Cheng Liu, Diane McKeone, Christophe Rosty, Ian Brown, …
Modern Pathology, Vol.31, pp.495-504
2018
DOI: https://doi.org/10.1038/modpathol.2017.150
url
https://doi.org/10.1038/modpathol.2017.150View
Published Version

Abstract

Medical and Health Sciences
Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively. WNT pathway activation was seen to a lesser extent in serrated pathway lesions. It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001). However, unlike the conventional pathway, truncating APC mutations were rare in the serrated pathway lesions especially sessile serrated adenomas even when dysplastic (15%) and in the BRAF mutant cancers with microsatellite instability that arise from them (8%). In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%). We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis. Moderate impact APC mutations and non-APC-related causes of increased WNT signaling may have a more important role in serrated neoplasia than the truncating APC mutations common in conventional adenomas.

Details

Metrics

2 File views/ downloads
250 Record Views
48 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types
Domestic collaboration
Web Of Science research areas
Pathology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

Source: InCites

Logo image