Parafibromin Abnormalities in Ossifying Fibroma

Abstract

Abstract Ossifying fibromas are very rare tumors that are sometimes seen as part of the hyperparathyroidism-jaw tumor syndrome (HPT-JT), which is caused by inactivating mutations of the HRPT2/CDC73 tumor suppressor gene. CDC73 mutations have been identified in a subset of sporadic cases but aberrant expression of the encoded protein, parafibromin, has not been demonstrated in ossifying fibroma. We sought to determine if loss of parafibromin regularly contributes to the development of sporadic, nonsyndromic ossifying fibroma. We examined a series of 9 ossifying fibromas, including ossifying, cemento-ossifying, and juvenile active variants, for parafibromin protein expression by immunohistochemistry and for CDC73 sequence abnormalities by Sanger sequencing and/or targeted AmpliSeq panel sequencing. Four ossifying fibromas showed a complete absence of nuclear parafibromin expression; loss of parafibromin expression was coupled with aberrant cytoplasmic parafibromin expression in 1 case. CDC73 mutations were detected in 2 cases with aberrant parafibromin expression. These results provide novel evidence, at the level of protein expression, that loss of the parathyroid CDC73/parafibromin tumor suppressor may play a role in the pathogenesis of a subset of ossifying fibromas.