HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

Background: Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1 alpha is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1 alpha expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. Methods: 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. Results: HIF-1 alpha was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1 alpha was related with a significantly improved 5-year survival rate ( p < 0.01) and a significantly increased disease free period ( p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1 alpha expression specified a subgroup of high-risk patients ( p < 0.05). Conclusion: HIF-1 alpha overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1 alpha expression may therefore be considered for adjuvant radiotherapy.