title: CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer.
abstract: Inactivating mutations of the CDC73 tumor suppressor gene have been reported in parathyroid carcinomas (PC), in association with the loss of nuclear expression of the encoded protein, parafibromin. The aim of this study was to further investigate the role of the CDC73 gene in PC and evaluate whether gene carrier status and/or the loss of parafibromin staining might have an effect on the outcome of the disease. We performed genetic and immunohistochemical studies in parathyroid tumor samples from 35 patients with sporadic PC. Nonsense or frameshift CDC73 mutations were detected in 13 samples suitable for DNA sequencing. Six of these mutations were germline. Loss of parafibromin expression was found in 17 samples. The presence of the CDC73 mutation as well as the loss of parafibromin predicted a high likelihood of subsequent recurrence and/or metastasis (92.3%, P=0.049 and 94.1%, P=0.0017 respectively), but only the latter was associated with a decreased overall 5- and 10-year survival rates (59%, P=0.107, and 23%, P=0.0026 respectively). The presence of both the CDC73 mutation and loss of parafibromin staining compared with their absence predicted a lower overall survival at 10- (18 vs 84%, P=0.016) but not at 5-year follow-up. In conclusion, loss of parafibromin staining, better than CDC73 mutation, predicts the clinical outcome and mortality rate. The added value of CDC73 mutational analysis is the possibility of identifying germline mutations, which will prompt the screening of other family members.
authors.affiliation: Department of Clinical and Experimental Medicine Section of PathologyDepartment of Oncology Department of SurgicalMedical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy Surgery UnitSurgical Oncology and Gastroenterology Sciences MedicineUniversity of Padua, Padua, Italy General Surgery 3 and Esophageal Surgery Clinical and Biological SciencesUniversity of Turin, Turin, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Cetani
authors.forename: Chiara
authors.initials: C
authors.lastname: Banti
authors.forename: Elena
authors.initials: E
authors.lastname: Pardi
authors.forename: Simona
authors.initials: S
authors.lastname: Borsari
authors.forename: Paolo
authors.initials: P
authors.lastname: Viacava
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Liborio
authors.initials: L
authors.lastname: Torregrossa
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Pelizzo
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Pennelli
authors.forename: Guido
authors.initials: G
authors.lastname: Gasparri
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Edda
authors.initials: E
authors.lastname: Vignali
authors.forename: Federica
authors.initials: F
authors.lastname: Saponaro
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
keywords: immunostaining; parathyroid tumorigenesis; primary hyperparathyroidism; survival