Parathyroid carcinoma: current understanding and new insights into gene expression and intraoperative parathyroid hormone kinetics.
Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma.
Adam
Mohamed Abdelgadir
MA
Jr., Duke University Medical Center, Durham, North Carolina 27710, USA. jaomd@duke.edu
Untch
Brian R
BR
Olson
John A
JA
D001706:Biopsy; D000069449:Cinacalcet; D003952:Diagnostic Imaging; D015870:Gene Expression; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology; D006961:Hyperparathyroidism / Q000209:etiology; D007150:Immunohistochemistry; D007430:Intraoperative Care; D008991:Monitoring, Physiologic; D009154:Mutation; D009281:Naphthalenes / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000097:blood*; D010282:Parathyroid Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D016105:Parathyroidectomy; D011379:Prognosis; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
C454900:CDC73 protein, human; D009281:Naphthalenes; D010281:Parathyroid Hormone; D025521:Tumor Suppressor Proteins; D000069449:Cinacalcet