title: Expression of parafibromin in distant metastatic parathyroid tumors in patients with advanced secondary hyperparathyroidism due to chronic kidney disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Transplant and Endocrine Surgery, Nagoya Second Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya 4668650, Japan. ytomi@nagoya2.jrc.or.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tominaga
authors.forename: Toyonori
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Susumu
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Uno
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Sato
authors.forename: Syuichi
authors.initials: S
authors.lastname: Shimabukuro
authors.forename: Norihiko
authors.initials: N
authors.lastname: Goto
authors.forename: Takaharu
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D016105:Parathyroidectomy; D006435:Renal Dialysis; D012189:Retrospective Studies; D013899:Thoracic Neoplasms / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins