Molecular profiles of oxyphilic and chief cell parathyroid adenoma.
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.
['Lu|Ming|M|', 'Kjellin|Hanna|H|', 'Fotouhi|Omid|O|', 'Lee|Linkiat|L|', 'Nilsson|Inga-Lena|IL|', 'Haglund|Felix|F|', 'Höög|Anders|A|', 'Lehtiö|Janne|J|', 'Larsson|Catharina|C|']
D018249:Adenoma, Oxyphilic D000293:Adolescent D000328:Adult D000367:Age Factors D000368:Aged D000369:Aged, 80 and over D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008875:Middle Aged D009363:Neoplasm Proteins D010281:Parathyroid Hormone D010282:Parathyroid Neoplasms D018167:Receptors, Calcitriol D055815:Young Adult
parathyroid adenoma LC-MS/MS Hyperparathyroidism Proteomic analysis