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Accuracy of Combined Protein Gene Product 9.5 and Parafibromin Markers for Immunohistochemical Diagnosis of Parathyroid Carcinoma
University of Sydney.
University of Sydney.
CSIRO, Australia.
University of Sydney.
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2009 (English)In: JOURNAL OF CLINICAL ENDOCRINOLOGY and METABOLISM, ISSN 0021-972X, Vol. 94, no 2, 434-441 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 94, no 2, 434-441 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-16854DOI: 10.1210/jc.2008-1740OAI: diva2:174397
Available from: 2009-02-21 Created: 2009-02-20 Last updated: 2009-08-18

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