Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma

J Clin Endocrinol Metab. 2009 Feb;94(2):434-41. doi: 10.1210/jc.2008-1740. Epub 2008 Nov 18.


Context: Parafibromin, encoded by HRPT2, is the first marker with significant benefit in the diagnosis of parathyroid carcinoma. However, because parafibromin is only involved in up to 70% of parathyroid carcinomas and loss of parafibromin immunoreactivity may not be observed in all cases of HRPT2 mutation, a complementary marker is needed.

Objective: We sought to determine the efficacy of increased expression of protein gene product 9.5 (PGP9.5), encoded by ubiquitin carboxyl-terminal esterase L1 (UCHL1) as an additional marker to loss of parafibromin immunoreactivity for the diagnosis of parathyroid carcinoma.

Design: In total, 146 parathyroid tumors and nine normal tissues were analyzed for the expression of parafibromin and PGP9.5 by immunohistochemistry and for UCHL1 by quantitative RT-PCR. These samples included six hyperparathyroidism-jaw tumor syndrome-related tumors and 24 sporadic carcinomas.

Results: In tumors with evidence of malignancy, strong staining for PGP9.5 had a sensitivity of 78% for the detection of parathyroid carcinoma and/or HRPT2 mutation and a specificity of 100%. Complete lack of nuclear parafibromin staining had a sensitivity of 67% and a specificity of 100%. PGP9.5 was positive in a tumor with the HRPT2 mutation L64P that expressed parafibromin. Furthermore, UCHL1 was highly expressed in the carcinoma/hyperparathyroidism-jaw tumor syndrome group compared to normal (P < 0.05) and benign specimens (P < 0.001).

Conclusion: These results suggest that positive staining for PGP9.5 has utility as a marker for parathyroid malignancy, with a slightly superior sensitivity (P = 0.03) and similar high specificity to that of parafibromin.

Publication types

  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry / methods
  • Models, Biological
  • Mutation / physiology
  • Neoplasm Staging
  • Parathyroid Neoplasms / diagnosis*
  • Parathyroid Neoplasms / genetics
  • Parathyroid Neoplasms / metabolism
  • Parathyroid Neoplasms / pathology
  • Sensitivity and Specificity
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin Thiolesterase / analysis
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism*


  • Biomarkers, Tumor
  • CDC73 protein, human
  • Tumor Suppressor Proteins
  • UCHL1 protein, human
  • Ubiquitin Thiolesterase