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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases
Journal of Clinical Pathology, Volume 73, No. 7, Year 2020
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Description
Aims Inflammatory bowel disease (IBD)-associated precancerous lesions may be adenomatous or non-adenomatous with various histomorphologies. We aim to validate the newly proposed classification, to explore the neoplastic nature of the non-adenomatous lesions and to elucidate the molecular mechanisms underlying the different histomorphologies. Methods 44 background precursor lesions identified in 53 cases of surgically resected IBD-associated colorectal and ileal carcinomas were reviewed for the histomorphological features (classified into adenomatous, mucinous, sessile serrated adenoma (SSA)-like, traditional serrated adenoma-like, differentiated, eosinophilic and serrated not otherwise specified (NOS)) and analysed for a key panel of colonic cancer-related molecular markers. Results Approximately 60% of the lesions were adenomatous, of which some had mixed serrated, mucinous or eosinophilic changes. The remaining non-adenomatous lesions, including all other types except SSA-like type, mostly showed mixed features and focal adenomatous dysplasia. KRAS mutation and p53 mutant-type expression were found in about half cases across all types, while PIK3CA mutation only in some of adenomatous and eosinophilic lesions and MLH1/PMS2 loss in a subset of adenomatous, mucinous and eosinophilic but not in differentiated and serrated lesions. SAT-B2 or PTEN loss and IMP3 overexpression were seen in a small subset of lesions. No BRAF, NRAS or EGFR gene mutation was detected in any type. Certain molecular-morphological correlations were demonstrated; however, no single or combined molecular alteration(s) was specific to any particular morphological type. Conclusions IBD-associated precancerous lesions are heterogeneous both histologically and molecularly. True colitis-associated adenomatous lesions are unlikely conventional adenomas. Non-adenomatous lesions without frank cytologic dysplasia should also be regarded as neoplastic. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Authors & Co-Authors
Gui, Xianyong
United States, Seattle
University of Washington School of Medicine
Canada, Calgary
University of Calgary
Köbel, Martin
Canada, Calgary
University of Calgary
Ghosh, Subrata
United Kingdom, Birmingham
Nihr Birmingham Biomedical Research Centre
Liu, Shuhong
Canada, Calgary
University of Calgary
Ou, Young
Canada, Calgary
University of Calgary
Rambau, Peter Fabian
Canada, Calgary
University of Calgary
Statistics
Citations: 27
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1136/jclinpath-2019-206247
ISSN:
00219746
Research Areas
Cancer
Genetics And Genomics