BACKGROUND: Recently, somatic inactivating mutations in HRPT2 have been reported in the majority of sporadic parathyroid carcinoma in primary hyperparathyroidism (HPT). Parafibromin is a tumor suppressor protein encoded by HRPT2, and loss of nuclear expression of parafibromin was found in approximately 70% of the carcinoma. In secondary HPT due to chronic kidney disease (CKD), parathyroid carcinoma is very rare and whether HRPT2 plays a role in the carcinogenesis in these cases is not clear. We evaluated the expression of parafibromin in hemodialysis patients with distant metastatic parathyroid tumors. METHODS: Between June 1973 and December 2006, 2,142 patients underwent parathyroidectomy (PTx) for secondary HPT in our department. We encountered five (0.23%) patients with distant metastatic parathyroid tumors. We evaluated the immunohistochemistry for parafibromin in eight primary parathyroid glands removed from the neck at the initial operation and/or at reoperation and seven distant metastatic tumors resected at reoperation. RESULTS: In only one lung metastatic parathyroid tumor, negative staining for parafibromin was detected. In the other three lung, two regional node, and one chest wall metastatic parathyroid tumor, parafibromin was strongly stained in the nuclei of the parathyroid cells. Among eight primary glands, except for one with weakly positive staining, the expression of parafibromin was detected diffusely and strongly. CONCLUSION: We conclude that the inactivating mutations and/or allelic loss of the HRPT2 gene may not play a major role in parathyroid carcinogenesis in secondary HPT due to CKD, but in these cases cancer development may be associated with a heterogeneous genetic disorder.
BACKGROUND: Recently, somatic inactivating mutations in HRPT2 have been reported in the majority of sporadic parathyroid carcinoma in primary hyperparathyroidism (HPT). Parafibromin is a tumor suppressor protein encoded by HRPT2, and loss of nuclear expression of parafibromin was found in approximately 70% of the carcinoma. In secondary HPT due to chronic kidney disease (CKD), parathyroid carcinoma is very rare and whether HRPT2 plays a role in the carcinogenesis in these cases is not clear. We evaluated the expression of parafibromin in hemodialysis patients with distant metastatic parathyroid tumors. METHODS: Between June 1973 and December 2006, 2,142 patients underwent parathyroidectomy (PTx) for secondary HPT in our department. We encountered five (0.23%) patients with distant metastatic parathyroid tumors. We evaluated the immunohistochemistry for parafibromin in eight primary parathyroid glands removed from the neck at the initial operation and/or at reoperation and seven distant metastatic tumors resected at reoperation. RESULTS: In only one lung metastatic parathyroid tumor, negative staining for parafibromin was detected. In the other three lung, two regional node, and one chest wall metastatic parathyroid tumor, parafibromin was strongly stained in the nuclei of the parathyroid cells. Among eight primary glands, except for one with weakly positive staining, the expression of parafibromin was detected diffusely and strongly. CONCLUSION: We conclude that the inactivating mutations and/or allelic loss of the HRPT2 gene may not play a major role in parathyroid carcinogenesis in secondary HPT due to CKD, but in these cases cancer development may be associated with a heterogeneous genetic disorder.
Authors: Maher W Khan; Elaine M Worcester; Francis H Straus; Shaher Khan; Victoria Staszak; Edwin L Kaplan Journal: J Am Coll Surg Date: 2004-08 Impact factor: 6.113
Authors: Y Tominaga; T Tsuzuki; K Uchida; T Haba; S Otsuka; T Ichimori; K Yamada; M Numano; Y Tanaka; H Takagi Journal: Kidney Int Date: 1999-04 Impact factor: 10.612
Authors: J D Carpten; C M Robbins; A Villablanca; L Forsberg; S Presciuttini; J Bailey-Wilson; W F Simonds; E M Gillanders; A M Kennedy; J D Chen; S K Agarwal; R Sood; M P Jones; T Y Moses; C Haven; D Petillo; P D Leotlela; B Harding; D Cameron; A A Pannett; A Höög; H Heath; L A James-Newton; B Robinson; R J Zarbo; B M Cavaco; W Wassif; N D Perrier; I B Rosen; U Kristoffersson; P D Turnpenny; L-O Farnebo; G M Besser; C E Jackson; H Morreau; J M Trent; R V Thakker; S J Marx; B T Teh; C Larsson; M R Hobbs Journal: Nat Genet Date: 2002-11-18 Impact factor: 38.330
Authors: K J Bradley; B M Cavaco; M R Bowl; B Harding; T Cranston; C Fratter; G M Besser; M Conceição Pereira; M W J Davie; N Dudley; V Leite; G P Sadler; A Seller; R V Thakker Journal: Clin Endocrinol (Oxf) Date: 2006-03 Impact factor: 3.478
Authors: Catherine Madorin; Randall P Owen; William D Fraser; Phillip K Pellitteri; Brian Radbill; Alessandra Rinaldo; Raja R Seethala; Ashok R Shaha; Carl E Silver; Matthew Y Suh; Barrie Weinstein; Alfio Ferlito Journal: Eur Arch Otorhinolaryngol Date: 2011-11-20 Impact factor: 2.503