title: Hypermethylation of adenosine triphosphate-binding cassette transporter genes in primary hyperparathyroidism and its effect on sestamibi imaging.
abstract: BACKGROUND
  Retention of technetium-(99m)-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
  The objective was to determine whether hypermethylation of either gene plays a role in their expression and (99m)Tc-sestamibi retention.
  
  
  METHODS
  This was a retrospective study on a convenience sample of paraffin-embedded parathyroid glands.
  
  
  METHODS
  The study was performed at the John Wayne Cancer Institute at Saint John's Health Center (Santa Monica, CA).
  
  
  METHODS
  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.
  
  
  METHODS
  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 (99m)Tc-sestamibi scan.
  
  
  METHODS
  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 (99m)Tc-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 (99m)Tc-sestamibi-positive scans (P < 0.001).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Greep
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.forename: Nora M
authors.initials: NM
authors.lastname: Hansen
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Umetani
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Singer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000236:Adenoma / Q000000981:diagnostic imaging / Q000473:pathology; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000000981:diagnostic imaging* / Q000235:genetics*; D007150:Immunohistochemistry; D008745:Methylation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010280:Parathyroid Glands / Q000000981:diagnostic imaging / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017256:Technetium Tc 99m Sestamibi
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012313:RNA; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; C421109:multidrug resistance-associated protein 1