title: Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma?
abstract: OBJECTIVE
  HRPT2 gene mutations are associated with parathyroid carcinomas, and absence of parafibromin immunoreactivity has been suggested as a diagnostic marker of malignancy. The aim of our study was to extend parafibromin studies in a series of benign and malignant parathyroid tumors and cross-validate the results of immunohistochemistry with those of HRPT2 analysis.
  
  
  METHODS
  We performed parafibromin and cyclin D1 immunostaining and HRPT2 gene analysis using loss of heterozygosity studies and sequencing analysis in parathyroid specimens from 11 patients with carcinoma (eleven primary tumors, one skin, and four lung metastases), 22 with sporadic adenomas, and 4 with atypical adenomas.
  
  
  RESULTS
  Ten out of eleven parathyroid cancers were negative for parafibromin staining and showed HRPT2 gene abnormalities. The remaining sample was negative for immunostaining and genetic analyses. All but one sporadic adenomas showed parafibromin immunoreactivity and no HRPT2 gene abnormalities. The sample with negative immunostaining carried an HRPT2 mutation. Two atypical adenomas were positive and two negative with parafibromin staining. No HRPT2 abnormalities were found in these samples. Cyclin D1 expression was heterogeneous and there was no relationship between expression/expression level of cyclin D1 and parafibromin expression.
  
  
  CONCLUSIONS
  We have shown that negative parafibromin staining is almost invariably associated with HRPT2 mutations and confirm that loss of parafibromin staining strongly predicts parathyroid malignancy. In clinical practice, these tests could be particularly useful in the subset of parathyroid tumors with equivocal histological examination. However, their diagnostic value in this setting remains to be proven.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. cetani@endoc.med.unipi.it
authors.forename: Filomena
authors.initials: F
authors.lastname: Cetani
authors.forename: Elena
authors.initials: E
authors.lastname: Ambrogini
authors.forename: Paolo
authors.initials: P
authors.lastname: Viacava
authors.forename: Elena
authors.initials: E
authors.lastname: Pardi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fanelli
authors.forename: Antonio Giuseppe
authors.initials: AG
authors.lastname: Naccarato
authors.forename: Simona
authors.initials: S
authors.lastname: Borsari
authors.forename: Monica
authors.initials: M
authors.lastname: Lemmi
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D000328:Adult; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: C454900:CDC73 protein, human; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1