Parathyroid Tumors: Molecular Signatures

Marini, Francesca; Giusti, Francesca; Iantomasi, Teresa; Brandi, Maria Luisa

doi:10.3390/ijms222011206

Cited by 15 publications

(23 citation statements)

References 66 publications

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“…Several genes have been identified in the pathogenesis of sporadic PA. The majority of PA are characterized by mutations in the MEN1 tumor suppressor gene located on chromosome 11q which is identified in 25% to 40% of cases 16,18,74,83 . MEN1 gene alterations are characterized predominantly by loss of heterozygosity with biallelic inactivation.…”

Section: Genetics Of Parathyroid Neoplasiamentioning

confidence: 99%

“…In one study utilizing whole-exome sequencing, a low frequency of EZH2 mutations were identified 89. Additional alterations include aberrant methylation of promoters of WT1 , APC , RASSF1A , SFRP1 , SFRP2 , and SFRP4 , although these have not been firmly established as drivers of tumorigenesis 16,83,90…”

Section: Genetics Of Parathyroid Neoplasiamentioning

confidence: 99%

“…89 Additional alterations include aberrant methylation of promoters of WT1, APC, RASSF1A, SFRP1, SFRP2, and SFRP4, although these have not been firmly established as drivers of tumorigenesis. 16,83,90 Parathyroid Carcinoma…”

Section: Genetics Of Parathyroid Neoplasia Sporadic Parathyroid Adenomasmentioning

confidence: 99%

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Advances and Updates in Parathyroid Pathology

Gokozan

Scognamiglio

2022

Advances in Anatomic Pathology

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Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.

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Section: Genetics Of Parathyroid Neoplasiamentioning

confidence: 99%

Section: Genetics Of Parathyroid Neoplasiamentioning

confidence: 99%

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Advances and Updates in Parathyroid Pathology

Gokozan

Scognamiglio

2022

Advances in Anatomic Pathology

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“…Genetic and epigenetic changes drive the development of parathyroid neoplasms [23][24][25] and influence the proteome. To assess the presence and cellular location of certain proteins, immunohistochemistry is an indispensable tool.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review

Uljanovs

Sinkarevs

Strumfs

et al. 2022

IJMS

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Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic CDC73 mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or up-regulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immunophenotype is not the final proof of malignancy but should prompt the search for the definitive criteria for carcinoma. Histogenetic studies can be necessary for differential diagnosis between thyroid vs. parathyroid origin of cervical or intrathyroidal mass; detection of parathyroid hormone (PTH), chromogranin A, TTF-1, calcitonin or CD56 can be helpful. Finally, immunohistochemistry is useful in pathogenetic studies due to its ability to highlight both the presence and the tissue location of certain proteins. The main markers and challenges (technological variations, heterogeneity) are discussed here in the light of the current WHO classification (2022) of parathyroid tumours.

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“…In addition, the mutational status of APC, RB, E-cadherin, MDM2 and p53 overexpression are considered useful biomarkers for parathyroid carcinomas’ diagnosis ( 7 ). Nevertheless, some PCas have an indolent growth and mimic benign lesions making their diagnosis more challenging ( 8 ). This clinical scenario is further complicated by the absence of accurate molecular markers supporting the differential diagnosis between parathyroid adenomas and carcinomas.…”

Section: Introductionmentioning

confidence: 99%

The Long Non-Coding BC200 Is a Novel Circulating Biomarker of Parathyroid Carcinoma

et al. 2022

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Long non-coding RNAs (lncRNAs) are an important class of epigenetic regulators involved in both physiological processes and cancer development. Preliminary evidence suggested that lncRNAs could act as accurate prognostic and diagnostic biomarkers. Parathyroid cancer is a rare endocrine neoplasia, whose management represents a clinical challenge due to the lack of accurate molecular biomarkers. Our previous findings showed that human parathyroid tumors are characterized by a different lncRNAs signature, suggesting heterogeneity through the different histotypes. Particularly, we found that the lncRNA BC200/BCYRN1 could represent a candidate biomarker for parathyroid carcinomas (PCas). Here we aimed to extend our preliminary data evaluating whether BC200 could be an accurate non-invasive biomarker of PCas to support the clinical management of patients affected by parathyroid tumors at diagnosis, prognosis and follow-up. To provide a non-invasive point-of-care for parathyroid carcinoma diagnosis and follow-up, we analyzed BC200 expression in patients’ serum through digital PCR. Our results show that BC200 counts are higher in serum from patients harboring PCa (n=4) compared to patients with parathyroid adenoma (PAd; n=27). Further, in PAd patients circulating BC200 levels are positively correlated with serum total calcium. Then, we found that BC200 is overexpressed in metastatic PCas (n=4) compared to non-metastatic ones (n=9). Finally, the lncRNA expression in PCa patients’ serum drops are reduced after parathyroidectomy, suggesting its possible use in the post-operative setting for patients follow-up. Overall, these findings extend the knowledge on BC200 in parathyroid tumors, supporting its role as a useful biomarker for management of PCa.

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Parathyroid Tumors: Molecular Signatures

Cited by 15 publications

References 66 publications

Advances and Updates in Parathyroid Pathology

Advances and Updates in Parathyroid Pathology

Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review

The Long Non-Coding BC200 Is a Novel Circulating Biomarker of Parathyroid Carcinoma

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