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Parathyroid Neoplasms: Immunohistochemical Characterization and Long Noncoding RNA (lncRNA) Expression

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Abstract

Parathyroid adenomas are slow growing benign neoplasms associated with hypercalcemia, while atypical parathyroid adenomas and parathyroid carcinomas are uncommon tumors and their histologic features may overlap with parathyroid adenomas. LncRNAs participate in transcription and in epigenetic or post-transcriptional regulation of gene expression, and probably contribute to carcinogenesis. We analyzed a group of normal, hyperplastic, and neoplastic parathyroid lesions to determine the best immunohistochemical markers to characterize these lesions and to determine the role of selected lncRNAs in tumor progression. A tissue microarray consisting of 111 cases of normal parathyroid (n = 14), primary hyperplasia (n = 15), secondary hyperplasia (n = 10), tertiary hyperplasia (n = 11), adenomas (n = 50), atypical adenomas (n = 7), and carcinomas (n = 4) was used. Immunohistochemical staining with antibodies against chromogranin A, synaptophysin, parathyroid hormone, and insulinoma-associated protein 1(INSM1) was used. Expression of lncRNAs including metastasis-associated lung adenocarcinoma transcript one (MALAT1), HOX transcript antisense intergenic RNA (HOTAIR), and long intergenic non-protein coding regulator of reprograming (Linc-ROR or ROR) was also analyzed by in situ hybridization and RT-PCR. All of the parathyroid tissues were positive for parathyroid hormone, while most cases were positive for chromogranin A (98%). Synaptophysin was expressed in only 12 cases (11%) and INMS1 was negative in all cases. ROR was significantly downregulated during progression from normal, hyperplastic, and adenomatous parathyroid to parathyroid carcinomas. These results show that parathyroid hormone and chromogranin A are useful markers for parathyroid neoplasms, while synaptophysin and INSM1 are not very sensitive broad-spectrum markers for these neoplasms. LincRNA ROR may function as a tumor suppressor during parathyroid tumor progression.

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Funding

The authors thank the Translational Research in Pathology (TRIP) Laboratory in the Department of Pathology and Laboratory Medicine and the University of Wisconsin Carbone Cancer Center support grant P30 CA014520 for support. Dr. Qiqi Yu received a resident research grant from the Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health.

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  1. Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI, 53792, USA

    Qiqi Yu, Heather Hardin, Ying-Hsia Chu, William Rehrauer & Ricardo V. Lloyd

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  1. Qiqi Yu
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  2. Heather Hardin
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  3. Ying-Hsia Chu
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  4. William Rehrauer
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  5. Ricardo V. Lloyd
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Correspondence to Ricardo V. Lloyd.

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The study was approved by the Institutional Review Board at the University of Wisconsin-Madison.

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Yu, Q., Hardin, H., Chu, YH. et al. Parathyroid Neoplasms: Immunohistochemical Characterization and Long Noncoding RNA (lncRNA) Expression. Endocr Pathol 30, 96–105 (2019). https://doi.org/10.1007/s12022-019-9578-3

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