Molecular profiles of oxyphilic and chief cell parathyroid adenoma.

Abstract

CONTEXT:

Parathyroid adenomas may be composed of chief cells (conventional or water-clear), oxyphilic cells or a mixture of both cells. The molecular background is rarely studied.

OBJECTIVE:

To molecularly characterize parathyroid adenomas of different cell type composition.

DESIGN:

Chief and oxyphilic cell adenomas were compared in a cohort of 664 sporadic cases. Extensive analyses of parathyroid tissues were performed in subgroup. Gene expressions of known parathyroid-related genes were quantified by qRT-PCR. Protein expression profiles determined by liquid chromatography - tandem mass spectrometry (LC-MS/MS) were compared between each type of parathyroid adenomas. Selected proteins were analysed by Western blot and immunohistochemistry.

RESULTS:

Patients with oxyphilic cell adenoma were found to be older at the time of operation than chief cell adenoma cases but did not differ in gender, serum calcium or tumor weight. The gene expression of CASR, VDR, FGFR1, CYP27B1, CYP24A1, PTHLH, GCM2, NDUFA13, CDKN1B, MEN1 and CNND1 did not differ between the groups. VDR protein levels were weaker in oxyphilic adenomas. The proteomic studies identified a set of novel dysregulated proteins of interest such as nuclear receptor subfamily 2 group C member 2 (TR4), LIM domain only protein 3 (LMO3) and calcium-binding protein B (S100B). LMO3 and S100B showed higher expression in oxyphilic adenoma and may be involve in parathyroid tumorgenesis through the p53 pathway. TR4 showed different subcellular localisation between adenoma and normal rim.

CONCLUSION:

Chief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development.

• Authors: Ming Lu, Hanna Kjellin, Omid Fotouhi, Linkiat Lee, Inga-Lena Nilsson, Felix Haglund, Anders Höög, Janne Lehtiö, Catharina Larsson
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 470 Pg. 84-95 (07 15 2018) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 28986304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Neoplasm Proteins
• Parathyroid Hormone
• Receptors, Calcitriol

Topics

• Adenoma, Oxyphilic (genetics, pathology)
• Adolescent
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)
• Parathyroid Hormone (genetics, metabolism)
• Parathyroid Neoplasms (genetics, pathology)
• Receptors, Calcitriol (metabolism)
• Young Adult