PMID- 38244045
OWN - NLM
STAT- Publisher
LR  - 20240120
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
DP  - 2024 Jan 20
TI  - Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and 
      clonally independent tumors.
LID - 10.1007/s00428-023-03730-3 [doi]
AB  - Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of 
      Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary 
      hyperplasia". Whether these tumors represent a multi-glandular clonal disease or 
      hyperplasia has not been robustly proven so far. Loss of Menin protein expression 
      is associated with inactivation of both alleles and a good surrogate for a MEN1 
      gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated 
      in MEN4 and encodes for protein p27 whose expression is poorly studied in the 
      syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression 
      of Menin and p27 in parathyroid adenomas of 25 patients of two independent, 
      well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was 
      assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated 
      parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on 
      eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 
      adenomas consisted of multiple distinct nodules, in which Menin expression was 
      mostly lost and p27 protein expression reduced. FISH analysis revealed that most 
      nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS 
      demonstrated both subclonal evolution and the existence of clonally unrelated 
      tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones 
      with subclones, which supports the current concept of the novel WHO 
      classification of parathyroid tumors (2022). p27 expression was lost in a large 
      fraction of MEN1 parathyroids and must therefore be used with caution in 
      suggesting MEN4.
CI  - (c) 2024. The Author(s).
FAU - Brautigam, Konstantin
AU  - Brautigam K
AD  - Institute of Tissue Medicine and Pathology, University of Bern, Murtenstr. 31, 
      3008, Bern, Switzerland. konstantin.braeutigam@unibe.ch.
FAU - Nesti, Cedric
AU  - Nesti C
AD  - Department of Visceral Surgery and Medicine, Inselspital, Bern University 
      Hospital, University of Bern, Bern, Switzerland.
FAU - Riss, Philipp
AU  - Riss P
AD  - Division of Visceral Surgery, Department of General Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Scheuba, Christian
AU  - Scheuba C
AD  - Division of Visceral Surgery, Department of General Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Niederle, Bruno
AU  - Niederle B
AD  - Division of Visceral Surgery, Department of General Surgery, Medical University 
      of Vienna, Vienna, Austria.
FAU - Grob, Tobias
AU  - Grob T
AD  - Institute of Tissue Medicine and Pathology, University of Bern, Murtenstr. 31, 
      3008, Bern, Switzerland.
FAU - Di Domenico, Annunziata
AU  - Di Domenico A
AD  - Institute of Tissue Medicine and Pathology, University of Bern, Murtenstr. 31, 
      3008, Bern, Switzerland.
FAU - Neuenschwander, Maja
AU  - Neuenschwander M
AD  - Institute of Tissue Medicine and Pathology, University of Bern, Murtenstr. 31, 
      3008, Bern, Switzerland.
FAU - Mazal, Peter
AU  - Mazal P
AD  - Department of Pathology, Medical University of Vienna, Vienna, Austria.
FAU - Kohn, Nastassja
AU  - Kohn N
AD  - Department of Visceral Surgery and Medicine, Inselspital, Bern University 
      Hospital, University of Bern, Bern, Switzerland.
AD  - Department of General Surgery, Cantonal Hospital of Aarau, Aarau, Switzerland.
FAU - Trepp, Roman
AU  - Trepp R
AD  - Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, 
      Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
FAU - Perren, Aurel
AU  - Perren A
AD  - Institute of Tissue Medicine and Pathology, University of Bern, Murtenstr. 31, 
      3008, Bern, Switzerland.
FAU - Kaderli, Reto M
AU  - Kaderli RM
AD  - Department of Visceral Surgery and Medicine, Inselspital, Bern University 
      Hospital, University of Bern, Bern, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20240120
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
SB  - IM
OTO - NOTNLM
OT  - Adenoma
OT  - MEN1
OT  - Menin
OT  - NGS
OT  - Parathyroid
OT  - p27
EDAT- 2024/01/20 21:41
MHDA- 2024/01/20 21:41
CRDT- 2024/01/20 11:13
PHST- 2023/08/18 00:00 [received]
PHST- 2023/12/26 00:00 [accepted]
PHST- 2023/12/11 00:00 [revised]
PHST- 2024/01/20 21:41 [medline]
PHST- 2024/01/20 21:41 [pubmed]
PHST- 2024/01/20 11:13 [entrez]
AID - 10.1007/s00428-023-03730-3 [pii]
AID - 10.1007/s00428-023-03730-3 [doi]
PST - aheadofprint
SO  - Virchows Arch. 2024 Jan 20. doi: 10.1007/s00428-023-03730-3.