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Transcription factor expression in selected giant cell lesions of the jaws

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand,
Johannesburg, in partial fulfillment of the requirements for the
Degree of
Master of Dentistry
In the branch of Oral Pathology
November 2012 / 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.

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/13798
Date11 1900
CreatorsBunn, Belinda Kathleen
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf

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