Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Green as soon as Postprint is submitted to ZB.
Loss of heterozygosity and absence of MAX immunostaining in a prolactinoma associated with multiple endocrine neoplasia type 5 (MEN5).
Pituitary 28:127 (2025)
BACKGROUND: Multiple endocrine neoplasia type 5 (MEN5) is an emerging syndrome caused by germline pathogenic variants involving the MYC Associated Factor X (MAX) gene. Affected individuals typically have pheochromocytomas, often bilateral, at a relatively early age. In MAX pheochromocytoma cohorts, pituitary adenomas are rarely reported. The role of MAX as a tumor suppressor gene in the pituitary gland has not been directly proven to date. METHODS: The propositus came from a pheochromocytoma kindred with a germline pathogenic MAX variant c.97 C>T (p.R33*). In his late thirties he developed asynchronous bilateral pheochromocytomas and underwent bilateral adrenalectomy. At age 46, he developed hyperprolactinemia (45.1 μg/L; 3x ULN) and increased IGF-1 (460 ng/mL; 1.9x ULN). Total testosterone was low (1.5 ng/mL) as was LH (1.2 IU/L). Pituitary MRI showed a microadenoma (6 mm), which was resected and his prolactin, IGF-1, and testosterone levels normalized. A Pituitary adenoma was confirmed on pathology, which showed positivity for prolactin only and a Ki67 of 2%. RESULTS: MAX immunohistochemical staining was lost in the pituitary adenoma cells. Tumoral DNA analysis (120X read depth) showed that at the MAX locus the pathogenic variant c.97 C>T constituted > 90% of the sequencing reads supporting tumoral loss of heterozygosity (LOH). CONCLUSIONS: Loss of MAX staining and the identification of tumor LOH at the MAX locus confirms pituitary adenomas as a component tumor in the emerging MEN5 syndrome due to germline pathogenic MAX variants.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genetics ; Max ; Men5 ; Pheochromocytoma ; Pituitary Adenoma; Mutations; Pheochromocytoma; Hereditary; Protein; Network; Complex
ISSN (print) / ISBN
1386-341X
e-ISSN
1573-7403
Journal
Pituitary
Quellenangaben
Volume: 28,
Issue: 6,
Article Number: 127
Publisher
Springer
Publishing Place
One New York Plaza, Suite 4600, New York, Ny, United States
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)