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¹ Departments of Molecular Medicine and Surgery and
² Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, CMM L8:01, SE-171 76 Stockholm, Sweden
³ Department of Endocrine Surgery, 8-1 Kawada-Cho, Sinjuku-Ku, Tokyo 162-8666, Japan
⁴ Center for Molecular Medicine and the Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, Connecticut 06030-3101, USA

(Requests for offprints should be addressed to C C Juhlin; Email: christofer.juhlin{at}ki.se)

Parafibromin is a protein product derived from the hyperparathyroidism 2(HRPT2) tumor suppressor geneand its inactivation has been coupled to familial and sporadic forms of parathyroid malignancy. In this study, we have conducted immunohistochemistry on 33 parathyroid carcinomas (22 unequivocal and 11 equivocal) using four parafibromin antibodies directed to different parts of the protein. Furthermore, for a fraction of cases, the immunohistochemical results were compared with known HRPT2 mutational status. Our findings show that 68% (15 out of 22) of the unequivocal carcinomas exhibited reduced expression of parafibromin while the 25 sporadic adenomas used as controls were entirely positive for parafibromin expression. Additionally, three out of the six carcinomas with known HRPT2 mutations showed reduced expression of parafibromin. Using all four antibodies, comparable results were obtained on the cellular level in individual tumors suggesting that there exists no epitope of choice in parafibromin immunohistochemistry. The results agree with the demonstration of a ~60 kDa product preferentially in the nuclear fraction by western blot analysis. We conclude that parafibromin immunohistochemistry could be used as an additional marker for parathyroid tumor classification, where positive samples have low risk of malignancy, whereas samples with reduced expression could be either carcinomas or rare cases of adenomas likely carrying an HRPT2 mutation.

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