Takeuchi Hiroya, Greep Nancy C, Hoon Dave S B, Giuliano Armando E, Hansen Nora M, Umetani Naoyuki, Singer Frederick R
Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
J Clin Endocrinol Metab. 2007 May;92(5):1785-90. doi: 10.1210/jc.2006-2010. Epub 2007 Feb 13.
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).
The objective was to determine whether hypermethylation of either gene plays a role in their expression and (99m)Tc-sestamibi retention.
This was a retrospective study on a convenience sample of paraffin-embedded parathyroid glands.
The study was performed at the John Wayne Cancer Institute at Saint John's Health Center (Santa Monica, CA).
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.
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.
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.
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).
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.
甲状旁腺腺瘤对锝-（99m）-司他米比（（99m）Tc-司他米比）的摄取似乎是由于至少一种膜转运蛋白——多药耐药蛋白1（MDR1）的缺失，也可能是另一种——多药耐药相关蛋白1（MRP1）的缺失。
目的是确定这两种基因的高甲基化是否在其表达及（99m）Tc-司他米比摄取中起作用。
这是一项对石蜡包埋甲状旁腺的便利样本进行的回顾性研究。
研究在圣约翰健康中心（加利福尼亚州圣莫尼卡）的约翰·韦恩癌症研究所进行。
48例原发性甲状旁腺功能亢进患者和5例接受甲状腺手术且无甲状旁腺疾病的患者提供了27个腺瘤性、10个增生性和16个正常甲状旁腺。
我们对存档的甲状旁腺组织进行了MDR1和MRP1的免疫组织化学、实时定量逆转录聚合酶链反应（RT-PCR）以及甲基化特异性PCR，并将这些结果与患者的（99m）Tc-司他米比扫描结果相关联。
主要观察指标是确定两种转运蛋白基因的高甲基化是否与它们的表达缺失以及（99m）Tc-司他米比扫描阳性相关。
12个正常腺体中无一例MDR1基因甲基化，27个腺瘤中有19个，10个增生性腺体中有3个。MRP1基因甲基化不常见（48个检测腺体中有5个）。基因甲基化仅影响MDR1的转录水平。在所有腺体中，MDR1高甲基化在（99m）Tc-司他米比阳性扫描中更常见（P<0.001）。
在甲状旁腺组织中，MDR1基因的高甲基化降低其表达，并与（99m）Tc-司他米比甲状旁腺扫描检测到更多甲状旁腺腺瘤相关。
