Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma.


PURPOSE A reliable method for diagnosing parathyroid carcinoma has remained elusive over the years, resulting in its under-recognition and suboptimal therapy. Obtaining an accurate diagnosis has become an even more pressing matter with recent evidence that germline HRPT2 gene mutations are found in patients with apparently sporadic parathyroid carcinoma. There is a high prevalence of HRPT2 gene mutations and biallelic inactivation in parathyroid carcinoma. We hypothesize that loss of parafibromin, the protein product of the HRPT2 gene, would distinguish carcinoma from benign tissue. EXPERIMENTAL DESIGN We generated a novel antiparafibromin monoclonal antibody and performed immunostaining on 52 definite carcinoma specimens, 6 equivocal carcinoma specimens, 88 benign specimens, and 9 hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from patients with primary hyperparathyroidism from nine worldwide centers and one national database. RESULTS We report that the loss of parafibromin nuclear immunoreactivity has 96% sensitivity [95% confidence interval (CI), 85-99%] and 99% specificity (95% CI, 92-100%) in diagnosing definite carcinoma. Inter-observer agreement for evaluation of parafibromin loss was excellent, with unweighted kappa of 0.89 (95% CI, 0.79-0.98). Two equivocal carcinomas misclassified as adenomas were highlighted by parafibromin immunostaining. One of these tumors has since recurred, satisfying criteria for a definite carcinoma. Similarly, eight of nine HPT-JT syndrome-related adenomas showed absent nuclear immunoreactivity. CONCLUSIONS Parafibromin is a promising molecular marker for diagnosing parathyroid carcinoma. The similar loss of parafibromin immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is a pivotal step in parathyroid tumorigenesis.

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@article{Tan2004LossOP, title={Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma.}, author={Min-Han Tan and Carl Morrison and Pengfei Wang and Ximing Yang and Carola J Haven and Chun Zhang and Ping Zhao and Maria S Tretiakova and Eeva Korpi-Hyovalti and John R Burgess and Khee Chee Soo and Wei-Keat Cheah and Brian Cao and James Resau and Hans Morreau and Bin Tean Teh}, journal={Clinical cancer research : an official journal of the American Association for Cancer Research}, year={2004}, volume={10 19}, pages={6629-37} }