This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Howell, V. M. Articles by Marsh, D. J. Search for Related Content PubMed PubMed Citation Articles by Howell, V. M. Articles by Marsh, D. J. Related Collections Calcium and Bone Metabolism Endocrine Oncology

Accuracy of Combined Protein Gene Product 9.5 and Parafibromin Markers for Immunohistochemical Diagnosis of Parathyroid Carcinoma

Kolling Institute of Medical Research (V.M.H., A.E.N., B.G.R., D.J.M.), Department of Anatomical Pathology (A.G., A.C.), and Endocrine Surgical Unit (L.W.D.), University of Sydney, Royal North Shore Hospital, St. Leonards, 2065 Australia; Commonwealth Scientific and Industrial Research Organization (R.D.), Mathematical and Information Sciences, North Ryde, 1670 Australia; Van Andel Research Institute (B.T.T.), Grand Rapids, Michigan 49503; and Department of Surgery (O.G.), University Hospital Linköping, SE-581 85 Linköping, Sweden

Address all correspondence and requests for reprints to: Deborah J. Marsh, Ph.D., Functional Genomics Laboratory, Hormones and Cancer Group, Kolling Institute of Medical Research, University of Sydney, Level 9, Kolling Building, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. E-mail: dmarsh{at}med.usyd.edu.au.

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.