Context: Retention of technetium-99-sestamibi (^99m-Tc-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: To determine whether hypermethylation of either gene plays a role in their expression and ^99m-Tc-sestamibi retention.

Design: A retrospective study on a convenience sample of paraffin-embedded parathyroid glands.

Setting: John Wayne Cancer Institute at Saint John's Health Center

Patients: Forty-eight patients with primary hyperparathyroidism and 5 patients without parathyroid disease undergoing thyroid surgery provided 27 adenomatous, 10 hyperplastic, and 16 normal parathyroid glands.

Intervention: We performed immunohistochemistry (IHC), real time quantitative polymerase chain reaction (qRT-PCR) and methylation-specific PCR for MDR1 and MRP1 on archival parathyroid tissue and correlated these results with the patient's ^99m-Tc-sestamibi scan.

Main Outcome Measures: To determine if hypermethylation of the genes for either transporter is associated with loss of their expression and with a positive ^99m-Tc-sestamibi scan.

Results: The MDR1 gene was methylated in none of 12 normal glands, 19 of 27 adenomas and 3 of 10 hyperplastic glands. Methylation of the MRP1 gene was uncommon (5 of 48 tested glands). Methylation of the gene affected the transcript level only for MDR1. Amongst all glands, hypermethylation for MDR1 was more likely in ^99m-Tc-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 ^99m-Tc-sestamibi parathyroid scans.