title: Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma.
abstract: BACKGROUND
  The origin and molecular pathogenesis of parathyroid carcinoma are unknown. This life-threatening cause of primary hyperparathyroidism cannot be reliably distinguished from its benign counterpart on the basis of histopathological features alone. Because the PRAD1, or cyclin D1, gene, a cell-cycle regulator, has been implicated in a subgroup of benign parathyroid tumors, we examined the possibility that another cell-cycle regulator with possible functional links to PRAD1, the retinoblastoma tumor-suppressor gene (RB), might be involved in the molecular pathogenesis of parathyroid carcinoma.
  
  
  METHODS
  Parathyroid carcinomas from 9 patients and adenomas from 21 were studied for evidence of tumor-specific loss of RB gene DNA (allelic loss) by analysis of four DNA polymorphisms and for evidence of altered expression oF RB protein by immunohistochemical staining.
  
  
  RESULTS
  All of 11 specimens from 5 patients with parathyroid carcinoma and informative DNA patterns and 1 of 19 specimens from 19 patients with parathyroid adenoma and informative DNA patterns lacked an RB allele. Fourteen of 16 specimens (88 percent) from the nine patients with carcinoma had abnormal expression of RB protein (a complete or predominant absence of nuclear staining for the protein). None of the 19 adenomas, including the tumor with loss of an RB allele, had unequivocally abnormal staining for RB protein.
  
  
  CONCLUSIONS
  Inactivation of the RB gene is common in parathyroid carcinoma and is likely to be an important contributor to its molecular pathogenesis. The presence of such inactivation may help to distinguish benign from malignant parathyroid disease and may have useful diagnostic, prognostic, and therapeutic implications.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston 02114.
authors.forename: V L
authors.initials: VL
authors.lastname: Cryns
authors.forename: A
authors.initials: A
authors.lastname: Thor
authors.forename: H J
authors.initials: HJ
authors.lastname: Xu
authors.forename: S X
authors.initials: SX
authors.lastname: Hu
authors.forename: M E
authors.initials: ME
authors.lastname: Wierman
authors.forename: A L
authors.initials: AL
authors.lastname: Vickery
authors.forename: W F
authors.initials: WF
authors.lastname: Benedict
authors.forename: A
authors.initials: A
authors.lastname: Arnold
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000483:Alleles; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D006801:Humans; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D016160:Retinoblastoma Protein