Tilakaratne, W.M., Iqbal, Z., Teh, M.T., Ariyawardana, A., Pitiyage, G., Cruchley, A., Stewart, J.E., Hagi-Pavli, E., Lalli, A., Waseem, A., Parkinson, E.K., and Fortune, F. (2008) Upregulation of HIF-1 alpha in malignant transformation of oral submucous fibrosis. Journal of Oral Pathology and Medicine, 37 (6). pp. 372-377.

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Abstract

Background: Oral submucous fibrosis (OSF) is a precancerous condition showing extensive fibrosis of the submucosa and affects most parts of the oral cavity, including pharynx and upper third of the oesophagus. The molecules involved in the biological pathways of the fibrotic process appeared to be either down- or upregulated at different stages of the disease. Despite the precancerous nature, malignant transformation of the epithelium in the background of fibrosis has not been studied in detail. HIF-1 alpha is a known transcription factor that is induced by hypoxia.

Aims: To test the hypothesis that hypoxia plays a role in malignant transformation and progression of OSF.

Materials and Methods: We used both formalin-fixed and frozen samples of OSF and normal mucosa to investigate the relationship between HIF-1 alpha and epithelial dysplasia using immunohistochemistry and RT-PCR.

Conclusions: Our data indicate that HIF-1 alpha is upregulated at both protein and mRNA levels in OSF and the correlation with epithelial dysplasia is statistically significant (P < 0.001). We propose that HIF-1 alpha may play a role in malignant transformation of OSF. Further, over-expression of HIF-1alpha may contribute to the progression of fibrosis. It may be possible to use HIF-1 alpha as a marker for malignant transformation of OSF.

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