Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

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Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases. / Gui, Xianyong; Kobel , Matin; Ferraz, Jose; Iacucci, Marietta; Ghosh, Subrata; Liu, Shuhong; Ou, Young; Perrizzolo, Marco; Winkfein , Robert; Rambau, Peter ; Demetrick, Douglas.

In: Journal of Clinical Pathology, 04.12.2019, p. 1-12.

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Gui, Xianyong ; Kobel , Matin ; Ferraz, Jose ; Iacucci, Marietta ; Ghosh, Subrata ; Liu, Shuhong ; Ou, Young ; Perrizzolo, Marco ; Winkfein , Robert ; Rambau, Peter ; Demetrick, Douglas. / Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases. In: Journal of Clinical Pathology. 2019 ; pp. 1-12.

Bibtex

@article{23ba66fb10b14a1a9743374be6df4f1b,
title = "Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases",
abstract = "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 = "Xianyong Gui and Matin Kobel and Jose Ferraz and Marietta Iacucci and Subrata Ghosh and Shuhong Liu and Young Ou and Marco Perrizzolo and Robert Winkfein and Peter Rambau and Douglas Demetrick",
year = "2019",
month = dec
day = "4",
doi = "10.1136/jclinpath-2019-206247",
language = "English",
pages = "1--12",
journal = "Journal of Clinical Pathology",
issn = "0021-9746",
publisher = "BMJ Publishing Group",

}

RIS

TY - JOUR

T1 - Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

AU - Gui, Xianyong

AU - Kobel , Matin

AU - Ferraz, Jose

AU - Iacucci, Marietta

AU - Ghosh, Subrata

AU - Liu, Shuhong

AU - Ou, Young

AU - Perrizzolo, Marco

AU - Winkfein , Robert

AU - Rambau, Peter

AU - Demetrick, Douglas

PY - 2019/12/4

Y1 - 2019/12/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85076136576&partnerID=8YFLogxK

U2 - 10.1136/jclinpath-2019-206247

DO - 10.1136/jclinpath-2019-206247

M3 - Article

SP - 1

EP - 12

JO - Journal of Clinical Pathology

JF - Journal of Clinical Pathology

SN - 0021-9746

ER -