Transcription factor expression in selected giant cell lesions of the jaws

Abstract

The giant cell lesions of the jaws are characterised histologically by scattered multinucleated giant cells (MNGCs) within a connective tissue stroma containing round and spindled mononuclear cells. Additional features include haemorrhage and haemosiderin deposition. Central giant cell granuloma (CGCG), peripheral giant cell granuloma (PGCG), cherubism and aneurysmal bone cyst (ABC) are thus encompassed by this term. The osteoclastic nature of the MNGCs within these lesions is well established. Microphthalmia-associated transcription factor (Mitf) is essential in the terminal differentiation of osteoclasts, the abnormal expression of which, results in dysfunctional osteoclast activity. Transcription factor E3 (Tfe3) belongs to the same transcription factor subfamily and is capable of forming co-immunoprecipitates with Mitf to function in a synergistic manner. It is abundantly expressed in physiological osteoclasts. Both factors are crucial for gene regulation in osteoclastic bone resorption. This study aimed to assess the expression of Mitf and Tfe3 within the stromal and MNGCs of the aforementioned giant cell lesions in order to enhance our understanding of the biological nature of these cells. The results showed positive nuclear staining within both the stromal and MNGCs in all four lesions with preferential expression noted in the MNGCs. This finding supports the concept of precursor stromal cell fusion. In addition, Mitf was consistently expressed at higher levels than Tfe3, in keeping with its reported principal role in the terminal differentiation process. The only exception to this was observed in ABC where Mitf and Tfe3 expression levels proved to be similar. It is thus apparent that the co-expression of Mitf and Tfe3 serves to confirm the osteoclast-like phenotype of the MNGCs within the giant cell lesions of the jaws. The degree of expression does not, however, correlate with the clinical behaviour of these cells, an observation substantiated by the minimal osteolytic potential of PGCG.