Expression of the Hypoxia Inducible Factor‐1 alpha in Head and Neck Squamous Cell Carcinoma

Problem: Hypoxia, a hallmark of solid tumors, functions as a driving force in cancer progression. The hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that is overexpressed in many human cancers and up-regulates genes that promote lethal tumor progression. Although significant associations between HIF-1alpha overexpression and patient mortality have been shown in most cancers, the function of HIF-1alpha in HNSCC tumor progression is controversial. Methods: Expression of HIF-1alpha was investigated by immunohistochemistry on paraffin-embedded sections from 34 patients with HNSCC and 9 patients with premalignant lesions. Results: HIF-1alpha was expressed in 85% of tumor sections with a nuclear expression pattern. The distribution of immunoreactive cells was independent of blood vessel and necrosis proximity, which indicates that factors other than hypoxia contribute to HIF-1alpha expression in HNSCC. Areas of hyperplasia adjacent to the tumor also showed nuclear reactivity; whereas none of the preinvasive isolated lesions show any HIF-1alpha expression. HIF-1alpha expression was significantly higher in advanced T-stage tumors (T4) compared with T1 tumors (P = 0.014). There was no significant difference in HIF-1alpha expression between categories of age, N-stage, histological grade, or localization. As primary tumors, paired lymph node metastases showed nuclear immunoreactivity to HIF-1alpha. There was a significant correlation between the percentage of HIF-1alpha positive cells in the primary tumor and the percentage in the corresponding metastasis (P = 0.006), suggesting a role of HIF-1alpha on cancer expansion. Conclusion: Our results suggest that HIF-1alpha expression in HNSCC is driven by an oxygen-independent mechanism, and that HIF-1alpha could contribute to the progression of these tumors. Significance: Overexpression of HIF-1alpha is a frequent event in HNSCC, suggesting that HIF-1alpha could be a therapeutic target in these carcinomas. Support: None reported.