The Study of Expression of Hypoxia-Inducible Factor-1 Alpha (HIF-1 Alpha) and Hypoxia- Inducible Factor-2 Alpha (HIF-2 Alpha) in Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Context: Oral cancer is the major cause of mortality and morbidity worldwide. There are many factors that influence the tumor microenvironment that promotes tumorigenesis. Hypoxia is one of the factors that affects the process of angiogenesis by inducing proangiogenic factors to maintain the blood supply which in turn enhances the aggressiveness of the tumor and prognosis of solid tumors such as oral squamous cell carcinoma.Aim and objective: The aim of the study was to compare the expression of hypoxia-inducible factor 1 alpha (HIF1 alpha) and hypoxia-inducible factor 2 alpha (HIF-2 alpha) in various histological grades of oral squamous cell carcinoma immunohistochemically.Methodology: Immunohistochemical evaluation of HIF-1 alpha and HIF-2 alpha was done in 90 samples of oral squamous cell carcinoma which were graded histologically into 30 samples each of well, moderately and poorly differentiated squamous cell carcinoma.Statistical evaluation: Statistical analysis was done to study the prognostic significance of the biomarkers.Results: All the cases showed positivity for expression of HIF-1 alpha and HIF-2 alpha. The number of positive staining in both markers reduced as the tumor severity increased from well to poorly differentiated. The expression of MIL of HIF-2 alpha was higher than HIF 1 alpha and HIF 2 alpha expression was mostly seen in cytoplasmic in well-differentiated and nuclear in both moderately and poorly differentiated OSCC suggestive that HIF2 alpha is a more specific marker to hypoxia. Conclusion: Hypoxia is an essential factor that triggers other angiogenic switch and inflammatory factors which facilitates the process of tumorigenesis. This is also important for predicting the treatment outcome and prognosis of the patients. HIF-2 alpha is a more sensitive marker that appears to be correlated and could perhaps serve as a good surrogate marker of hypoxia.