Upregulation of HIF-1alpha in malignant transformation of oral submucous fibrosis.
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-1alpha is a known transcription factor that is induced by hypoxia.


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


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


CONCLUSIONS
Our data indicate that HIF-1alpha 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-1alpha 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-1alpha as a marker for malignant transformation of OSF.
Tilakaratne
W M
WM
Clinical and Diagnostic Oral Sciences, Queen Mary's School of Medicine and Dentistry, University of London, London, UK. wmtilak@pdn.ac.lk
Iqbal
Z
Z
Teh
M T
MT
Ariyawardana
A
A
Pitiyage
G
G
Cruchley
A
A
Stewart
J E
JE
Hagi-Pavli
E
E
Lalli
A
A
Waseem
A
A
Parkinson
E K
EK
Fortune
F
F
D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic / Q000737:chemistry* / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000378:metabolism; D009914:Oral Submucous Fibrosis / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit