title: CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort.
abstract: OBJECTIVE
  To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort.
  
  
  METHODS
  Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n = 15), atypical adenoma (AA) (n = 14) and typical adenoma (TA) (n = 17), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations. IHC staining for parafibromin was performed and scored as positive if nuclear staining was at least partially IHC-positive.
  
  
  RESULTS
  Mutations of CDC73 were observed in 9/15 (60 %) CA, 2/14 (14 %) AA, and 1/17 (6 %) TA tumors. A recurrent two basepair mutation in exon 7 -- c.679_680delAG -- accounted for half of all identified mutations. Absence of parafibromin nuclear staining was noted in 8/12 (67 %) CA, 2/13 (15 %) AA, and 3/17 (18 %) TA tumors. Median follow up times were 88 months for CA, 76 months for AA, and 104 months for TA patients. One patient, a member of a previously reported multiplex family with a germline CDC73 mutation was found to have a second adenoma after removal of an atypical adenoma.
  
  
  CONCLUSIONS
  Molecular screening and IHC are both useful tools in the differential diagnosis of parathyroid tumors, but both have limited sensitivity and specificity. CDC73 mutations and negative immunostaining were common in atypical adenomas, but no local recurrence was observed in any case with successful surgical removal after follow-up periods of 27 to 210 months.
authors.affiliation: Genetics Unit, Ospedale "Casa Sollievo della Sofferenza", Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Guarnieri
authors.forename: Claudia
authors.initials: C
authors.lastname: Battista
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.forename: Michele
authors.initials: M
authors.lastname: Bisceglia
authors.forename: Danilo
authors.initials: D
authors.lastname: de Martino
authors.forename: Filomena
authors.initials: F
authors.lastname: Baorda
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.forename: Leonardo
authors.initials: L
authors.lastname: D'Agruma
authors.forename: Iacopo
authors.initials: I
authors.lastname: Chiodini
authors.forename: Celeste
authors.initials: C
authors.lastname: Clemente
authors.forename: Salvatore
authors.initials: S
authors.lastname: Minisola
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Romagnoli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Corbetta
authors.forename: Raffaella
authors.initials: R
authors.lastname: Viti
authors.forename: Cristina
authors.initials: C
authors.lastname: Eller-Vainicher
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
authors.forename: Michela
authors.initials: M
authors.lastname: Iacobellis
authors.forename: Nazzarena
authors.initials: N
authors.lastname: Malavolta
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Lucie
authors.initials: L
authors.lastname: Canaff
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Hendy
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
authors.forename: Alfredo
authors.initials: A
authors.lastname: Scillitani
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins