Central giant cell granuloma of the jaws: assessment of cell cycle proteins

BACKGROUND: Several reports have demonstrated the presence of a high proliferative activity in central giant cell granuloma, raising the possibility that deregulation of the cell cycle may contribute to its pathogenesis. As we identified alterations of cyclin D1 in giant cell tumor of bone, and as there are histologic similarities between central giant cell granuloma and giant cell tumor, we assessed jaw lesions for the presence of similar alterations. METHODS: Formalin-fixed, paraffin-embedded tissue from 29 cases of central giant cell granuloma was assessed for the expression of cyclin D1, cyclin B1, and MIB-1 (Ki-67) using immunohistochemistry. In addition, differential polymerase chain reaction (PCR) was used to determine whether there was cyclin D1 gene amplification. RESULTS: The cyclin D1 gene copy number appeared to be minimally elevated in 31% of the cases. Cyclin D1 protein overexpression was observed in 28 of 29 cases (96.5%). Immunostaining was present predominantly in the nuclei of the giant cells. Cyclin B1 and MIB-1 immunoreactivity was restricted to the mononuclear cells with no staining present in the giant cells. CONCLUSIONS: Cyclin D1 protein overexpression may be involved in the formation of the giant cells and the pathogenesis of central giant cell granuloma. As the distribution of immunostaining is identical to that observed in giant cell tumor of bone, our results support the possibility that central giant cell granuloma of the jaws and giant cell tumor of bone represent a similar disease process that clinically and histologically may have somewhat different features because of differences in the anatomical site of involvement.