Hypermethylation of adenosine triphosphate-binding cassette transporter genes in primary hyperparathyroidism and its effect on sestamibi imaging

Hiroya Takeuchi, Nancy C. Greep, Dave S.B. Hoon, Armando E. Giuliano, Nora M. Hansen, Naoyuki Umetani, Frederick R. Singer

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2 Citations (Scopus)

Abstract

Context: Retention of technetium-99m-sestamibi ( 99mTc-sestamibi) by parathyroid adenomas appears to be due to the loss of at least one membrane transporter, multidrug resistance 1 (MDR1), and possibly another, multidrug resistance-associated protein 1 (MRP1). Objective: The objective was to determine whether hypermethylation of either gene plays a role in their expression and 99mTc-sestamibi retention. Design: This was a retrospective study on a convenience sample of paraffin-embedded parathyroid glands. Setting: The study was performed at the John Wayne Cancer Institute at Saint John's Health Center (Santa Monica, CA). Patients: Forty-eight patients with primary hyperparathyroidism and five patients without parathyroid disease undergoing thyroid surgery provided 27 adenomatous, 10 hyperplastic, and 16 normal parathyroid glands. Intervention: We performed immunohistochemistry, real-time quantitative RT-PCR, and methylation-specific PCR for MDR1 and MRP1 on archival parathyroid tissue and correlated these results with the patient's 99mTc-sestamibi scan. Main Outcome Measure: The main outcome measure was to determine whether hypermethylation of the genes for either transporter is associated with loss of their expression and with a positive 99mTc-sestamibi scan. Results: The MDR1 gene was methylated in none of 12 normal glands, 19 of 27 adenomas, and three of 10 hyperplastic glands. Methylation of the MRP1 gene was uncommon (five of 48 tested glands). Methylation of the gene affected the transcript level only for MDR1. Among all glands, hypermethylation for MDR1 was more likely in 99mTc-sestamibi-positive scans (P < 0.001). Conclusion: In parathyroid tissue, hypermethylation of the MDR1 gene decreases its expression and is associated with increased detection of parathyroid adenomas by 99mTc-sestamibi parathyroid scans.

Original languageEnglish
Pages (from-to)1785-1790
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number5
DOIs
Publication statusPublished - 2007 May

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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