Risk Prediction for Malignant Conversion of Oral Epithelial Dysplasia by Hypoxia Related Protein Expression

Aims: Increased aerobic glycolysis is a unique finding in cancers and hypoxia-related proteins are associated with aerobic glycolysis. Therefore, we aimed to investigate whether hypoxia-related proteins can be predictive markers for malignant conversion of oral premalignant lesions with epithelial dysplasia (OED).

Methods: Expression of HIF-1α, Glut-1 and CA9 were detected in clinical samples of eight normal oral mucosa, 85 transitional areas of oral squamous cell carcinoma (OSCC) and 28 OED with or without malignant conversion using immunohistochemistry and were also comparatively detected in immortalised human oral keratinocyte (IHOK) and OSCC cell lines under hypoxia using immunoblotting.

Results: Sequential expression of HIF-1α, Glut-1 and CA9 was found both in transitional areas of OSCC and cell lines of IHOK and OSCC under hypoxia, supporting hypoxia-aerobic glycolysis-acidosis axis. Expression of all proteins showed significant association with malignant conversion of OED and CA9 was an independent risk factor of malignant transformation of OED. But the predictability of malignant transformation was improved when all three proteins were applied together.

Conclusion: High expression of CA9 was an independent predictive marker of malignant conversion. Moreover, the combined application of these three proteins may be useful to assess the risk of malignant conversion of OED.