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Intratumor heterogeneity in human parathyroid tumors
C Verdelli1, G S Tavanti1, S Corbetta2,3
1Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
Histology and Histopathology
|May 30, 2020
Summary
Parathyroid tumors, often benign, cause primary hyperparathyroidism (PHPT). Recent findings reveal significant intratumor heterogeneity in cell type and function, impacting PHPT
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Parathyroid tumors are the second most common endocrine neoplasia, primarily causing primary hyperparathyroidism (PHPT).
- PHPT, the third most prevalent endocrine disorder, predominantly affects postmenopausal women and is mainly linked to parathyroid adenomas or hyperplasia.
Purpose of the Study:
- To explore the concept of intratumor heterogeneity in parathyroid lesions.
- To investigate how this heterogeneity influences parathyroid tumor cell type, function, and molecular biology.
- To highlight the clinical implications of parathyroid tumor heterogeneity in managing PHPT.
Main Methods:
- Review of existing evidence on parathyroid tumor characteristics.
- Analysis of molecular markers including gene and microRNA expression.
- Examination of receptor expression patterns (calcium sensing receptor, vitamin D receptor, α-klotho).
Main Results:
- Parathyroid adenomas and hyperplasia exhibit significant intratumor heterogeneity.
- Heterogeneity extends to cell type, parathyroid hormone (PTH) synthesis/secretion, and receptor expression.
- Variations in clonality, oncosuppressor gene expression (MEN1, HRPT2/CDC73), transcription factors, and microRNAs are observed.
Conclusions:
- Intratumor heterogeneity is a key factor in the variable presentation of parathyroid tumors.
- Understanding this heterogeneity is crucial for clinical management, despite current limitations in targeted therapies.
- Further research into targeted therapies, potentially including calcium sensing receptor agonists, is warranted.
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