Overexpression of Hypoxia-Inducible Factor-1α and Its Relation with Aggressiveness and Grade of Oral Squamous Cell Carcinoma

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) has been shown to be involved in cancer metastasis in several cancer types. There is however conflicting evidence of HIF-1 alpha expression with oral cancer prognosis. Therefore, this study set out to investigate HIF-1 alpha overexpression and its relationship with the aggressiveness and grade of oral squamous cell carcinoma (OSCC) and to explore the diagnostic potential of HIF-1 alpha overexpression in OSCC in a cohort of Pakistani patients. Immunostaining of HIF-1 alpha was performed on 54 OSCC and 14 normal oral mucosa (NOM) tissue samples and various cut-offs were used to evaluate its immunohistochemical expression. HIF-1 alpha expression in OSCC samples was significantly higher than in controls, with minimal immunoreactivity in NOM. HIF-1 alpha overexpression was significantly associated with increased tumor size (p = 0.046). However, no association was found between HIF-1 alpha overexpression and increasing Broder's histological grade or TNM stage. The cut-off >10% cells with moderate to marked intensity carried a sensitivity of 70% and a specificity of 100% to distinguish between tumor and control. ROC curve analysis of HIF-1 alpha weighted histoscores showedHIF-1 alpha overexpression as a highly sensitive and specific diagnostic test (p < 0.001, AUC = 0.833). HIF-1 alpha overexpression is a tumor-specific finding associated with increased tumor size and carries a potential diagnostic role.