Epigenetic Dysregulation of 5-hydroxymethylcytosine in Well-Differentiated Pancreatic Neuroendocrine Tumors.
Journal
Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
16
06
2021
accepted:
14
09
2021
pubmed:
30
10
2021
medline:
3
5
2022
entrez:
29
10
2021
Statut:
ppublish
Résumé
Dysregulation of epigenetic mechanisms, reflected by loss of expression of 5-hydroxymethylcytosine (5-hmC) is being increasingly recognized as a marker of aggressive behavior in several neoplasms; however, the role of such epigenetic modifiers in pancreatic neuroendocrine tumors (PanNETs) has not been studied. Annotated cohort of 60 PanNETs was evaluated for 5-hmC expression using immunohistochemistry. Univariable and multivariable analyses were performed. To determine intratumor heterogeneity of 5-hmC expression, 26 additional synchronous metastatic deposits of PanNETs from 8 patients were evaluated for 5-hmC expression. 5-hmC level showed significant association with the presence of distant metastases (P=0.02), female sex (P=0.04), and Ki-67 proliferation index (P=0.002). A multivariate model created using the stepwise logistic regression analysis showed the presence of nodal metastases (odds ratio=6.15), lymphovascular invasion (odds ratio=4.07) and lack of 5-hmC expression (odds ratio=5.34) were predictive of the risk of distant metastasis in PanNETs with a c-statistic of 0.845. Epigenetic intratumoral heterogeneity of 5-hmC expression was seen in 37.5% cases (3/8). Our work provides evidence that epigenetic regulators are involved in the pathobiology of PanNETs and immunohistochemical analysis of 5-hmC may be able to refine prognostic evaluation of these tumors.
Identifiants
pubmed: 34711739
doi: 10.1097/PAI.0000000000000982
pii: 00129039-202202000-00012
doi:
Substances chimiques
5-hydroxymethylcytosine
1123-95-1
5-Methylcytosine
6R795CQT4H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e11-e15Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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