Metastatic Patterns of Duodenopancreatic Neuroendocrine Tumors in Patients With Multiple Endocrine Neoplasia Type 1.
Adult
Aged
Biomarkers, Tumor
/ analysis
Carcinoma, Neuroendocrine
/ chemistry
Databases, Factual
Duodenal Neoplasms
/ chemistry
Female
Gastrins
/ analysis
Homeodomain Proteins
/ analysis
Humans
Ki-67 Antigen
/ analysis
Lymphatic Metastasis
Male
Middle Aged
Multiple Endocrine Neoplasia Type 1
/ chemistry
Neoplasm Grading
Pancreatic Neoplasms
/ chemistry
Trans-Activators
/ analysis
Transcription Factors
/ analysis
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
pubmed:
25
9
2021
medline:
15
2
2022
entrez:
24
9
2021
Statut:
ppublish
Résumé
Patients with multiple endocrine neoplasia 1 syndrome (MEN1) often develop multifocal duodenopancreatic neuroendocrine tumors (dpNETs). Nonfunctional pancreatic neuroendocrine tumors (PanNETs) and duodenal gastrinomas are the most frequent origins of metastasis. Current guidelines recommend surgery based on tumor functionality, size ≥2 cm, grade or presence of lymph node metastases. However, in case of multiple primary tumors it is often unknown which specific tumor metastasized. This study aims to unravel the relationship between primary dpNETs and metastases in patients with MEN1 by studying endocrine differentiation. First, it was shown that expression of the endocrine differentiation markers ARX and PDX1 was concordant in 18 unifocal sporadic neuroendocrine tumors (NETs) and matched metastases. Thereafter, ARX, PDX1, Ki67 and gastrin expression, and the presence of alternative lengthening of telomeres were determined in 137 microscopic and macroscopic dpNETs and 36 matched metastases in 10 patients with MEN1. ARX and PDX1 H-score clustering was performed to infer relatedness. For patients with multiple metastases, similar intrametastases transcription factor expression suggests that most metastases (29/32) originated from a single NET of origin, while few patients may have multiple metastatic primary NETs. In 6 patients with MEN1 and hypergastrinemia, periduodenopancreatic lymph node metastases expressed gastrin, and clustered with minute duodenal gastrinomas, not with larger PanNETs. PanNET metastases often clustered with high grade or alternative lengthening of telomeres-positive primary tumors. In conclusion, for patients with MEN1-related hypergastrinemia and PanNETs, a duodenal origin of periduodenopancreatic lymph node metastases should be considered, even when current conventional and functional imaging studies do not reveal duodenal tumors preoperatively.
Identifiants
pubmed: 34560682
doi: 10.1097/PAS.0000000000001811
pii: 00000478-202202000-00002
doi:
Substances chimiques
ARX protein, human
0
Biomarkers, Tumor
0
Gastrins
0
Homeodomain Proteins
0
Ki-67 Antigen
0
MKI67 protein, human
0
Trans-Activators
0
Transcription Factors
0
pancreatic and duodenal homeobox 1 protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
159-168Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: Funded by Maag Darm Lever Stichting (Dutch Digestive Foundation) CDG 14-020. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
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