Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors.

Bräutigam, Konstantin; Nesti, Cédric; Riss, Philipp; Scheuba, Christian; Niederle, Bruno; Grob, Tobias; Di Domenico, Annunziata; Neuenschwander, Maja; Mazal, Peter; Köhn, Nastassja; Trepp, Roman; Perren, Aurel; Kaderli, Reto M (2024). Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors. Virchows Archiv, 484(5), pp. 789-798. Springer 10.1007/s00428-023-03730-3

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Bräutigam, Konstantin, Nesti, Cédric, Grob, Tobias, Di Domenico, Annunziata, Neuenschwander, Maja, Köhn, Olga Gertrud Nastassja, Trepp, Roman, Perren, Aurel, Kaderli, Reto Martin

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0945-6317

Publisher:

Springer

Language:

English

Submitter:

Pubmed Import

Date Deposited:

22 Jan 2024 07:27

Last Modified:

21 May 2024 00:13

Publisher DOI:

10.1007/s00428-023-03730-3

PubMed ID:

38244045

Uncontrolled Keywords:

Adenoma MEN1 Menin NGS Parathyroid p27

BORIS DOI:

10.48350/191949

URI:

https://boris.unibe.ch/id/eprint/191949

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