Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer.

TLDR

Hypoxia has long been recognized as detrimental to the successful treatment of malignant tumors with ionizing radiation. The study investigated whether HIF‑1α expression predicts outcomes in 98 patients with oropharyngeal squamous cell carcinoma treated with curative radiotherapy. HIF‑1α, a key regulator of oxygen homeostasis, was evaluated by immunohistochemistry in tumor samples. HIF‑1α was overexpressed in 94 % of tumors, and higher expression correlated with lower complete remission rates, increased lymph node metastases, and poorer local failure‑free, disease‑free, and overall survival; multivariate analysis confirmed its independent predictive value.

Abstract

Hypoxia has long been recognized as detrimental to the successful treatment of malignant tumors with ionizing radiation. Because hypoxia-inducible factor (HIF)-1alpha plays an essential role in oxygen homeostasis in vitro, we explored the predictive potential of this factor in a cohort of 98 patients with squamous cell cancer of the oropharynx, who were treated by curative radiation therapy. Ninety-four % of the primary tumors showed overexpression of HIF-1alpha, relative to the surrounding tissue, as determined by immunohistochemistry. The degree of HIF-1alpha immunoreactivity correlated inversely with both the rate of complete remission of the primary tumor (odds ratio, 0.33; P = 0.03) and lymph node metastases (odds ratio, 0.34; P = 0.02) as well as with local failure-free survival (risk ratio, 2.15; P = 0.006), disease-free survival (risk ratio, 2.01; P = 0.008), and overall survival (risk ratio, 2.17; P = 0.002). The multivariate analysis revealed the predictive power of HIF-1alpha to be independent of other covariables. We conclude that HIF-1alpha is overexpressed in the vast majority of patients with squamous cell cancer of the oropharynx and that the degree of expression has predictive and prognostic significance in individuals undergoing curative radiation therapy.