PMID- 34560682
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20230922
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 46
IP  - 2
DP  - 2022 Feb 1
TI  - Metastatic Patterns of Duodenopancreatic Neuroendocrine Tumors in Patients With 
      Multiple Endocrine Neoplasia Type 1.
PG  - 159-168
LID - 10.1097/PAS.0000000000001811 [doi]
AB  - 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.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Hackeng, Wenzel M
AU  - Hackeng WM
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht University.
FAU - van Beek, Dirk-Jan
AU  - van Beek DJ
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht.
FAU - Kok, Aranxa S M
AU  - Kok ASM
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht University.
FAU - van Emst, Madelon
AU  - van Emst M
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht University.
FAU - Morsink, Folkert H M
AU  - Morsink FHM
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht University.
FAU - van Treijen, Mark J C
AU  - van Treijen MJC
AD  - Department of Endocrine Oncology, University Medical Center Utrecht Cancer 
      Center, Utrecht.
FAU - Borel Rinkes, Inne H M
AU  - Borel Rinkes IHM
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht.
FAU - Dreijerink, Koen M A
AU  - Dreijerink KMA
AD  - Department of Endocrinology and Internal Medicine, Amsterdam University Medical 
      Centers, Amsterdam, The Netherlands.
FAU - Offerhaus, G Johan A
AU  - Offerhaus GJA
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht University.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht Cancer 
      Center, Utrecht.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht.
FAU - Brosens, Lodewijk A A
AU  - Brosens LAA
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht University.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (ARX protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Gastrins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (MKI67 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (pancreatic and duodenal homeobox 1 protein)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/analysis
MH  - Carcinoma, Neuroendocrine/chemistry/genetics/*secondary
MH  - Databases, Factual
MH  - Duodenal Neoplasms/chemistry/genetics/*pathology
MH  - Female
MH  - Gastrins/analysis
MH  - Homeodomain Proteins/analysis
MH  - Humans
MH  - Ki-67 Antigen/analysis
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/chemistry/genetics/*pathology
MH  - Neoplasm Grading
MH  - Pancreatic Neoplasms/chemistry/genetics/*pathology
MH  - Trans-Activators/analysis
MH  - Transcription Factors/analysis
COIS- 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.
EDAT- 2021/09/25 06:00
MHDA- 2022/02/15 06:00
CRDT- 2021/09/24 20:33
PHST- 2021/09/25 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/09/24 20:33 [entrez]
AID - 00000478-202202000-00002 [pii]
AID - 10.1097/PAS.0000000000001811 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2022 Feb 1;46(2):159-168. doi: 10.1097/PAS.0000000000001811.