Role of hypoxia in malignant transformation of oral submucous fibrosis

Abstract

Context: In the Indian subcontinent and Southeast Asia, habit of chewing areca nut has been recognized as one of the most important risk factors leading to a ubiquitous oral potentially malignant disorder (OPMD), oral submucous fibrosis (OSMF).In OSMF, owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu. This tissue hypoxia elicits the activation of the transcription factor Hypoxia-inducible factor 1-alpha (HIF-1 α). In OSMF, its expression shows significant correlation with degree of epithelial dysplasia. Aim: This study aims to evaluate the expression of HIF-1 α in OSMF. Settings and Design: Seventy-five histopathologically proven cases of OSMF were included in the study. The tissue sections were studied for histopathological evaluation and HIF-1α expression. Statistical Analysis Used: Descriptive and inferential statistics using one-way ANOVA and multiple comparison using Kruskal–Wallis test were used. Results: Comparison of HIF-1α expression in different grades of OSMF was done. There were 47 cases without dysplasia, whereas 16 and 12 were of low-risk and high-risk dysplasia, respectively. On comparison of HIF-1α expression in different grades of OSMF, it was found to increase significantly from normal oral mucosa (1.43 ± 0.89) to no dysplasia (3.97 ± 2.75) to low-risk epithelial dysplasia (4.93 ± 1.76) to high-risk epithelial dysplasia (5.66 ± 2.01). Conclusion: The altered expression of HIF-1α can signify the disturbed epithelial-mesenchymal interaction which indicates progression toward the malignant transformation of OSMF. Thus, HIF-1 α expression showed good correlation with increase in grades of epithelial dysplasia and thus can assist for grading/quantifying oral epithelial dysplasia in OSMF.