Clinical significance of HIF-1alpha expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

AIM

We investigated whether hypoxia-inducible factor-1α (HIF-1 α) expression in pretreatment biopsies of esophageal cancer is predictive of clinical outcome in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT).

PATIENTS AND METHODS

A total of 25 patients were reviewed. Radiotherapy was administered to total doses of 40-66.6 Gy (median: 66.6 Gy) with a single fraction of 1.8-2 Gy. Cisplatin (80 mg/m2 on day 1) and 5-fluorouracil (800 mg/m2 on days 2-6) were administered concurrently with radiotherapy, every 3-4 weeks to a total of 1-2 courses. Tissue samples from esophageal cancer were obtained from all 25 patients by biopsy before concurrent CRT, and semiquantitative analyses of HIF-1α expression were performed using immunohistochemical staining.

RESULTS

High HIF-1α expression was observed in 11 out of 25 patients (42.7%), and HIF-1α expression was significantly correlated with initial response to CRT (p=0.0027). Patients with high HIF-1α expression had significantly poorer local control (LC) (5-year LC: 42.7%) than those with low expression (5-year LC: 72.5%; p=0.0322). Patients with high HIF-1α expression also had significantly lower recurrence-free survival (RFS) (5-year RFS: 18.2%) compared to those with low HIF-1α expression (5-year RFS: 39.8%; p=0.0009), and on multivariate analysis, HIF-1α (p=0.001) and number of chemotherapy courses (p=0.010) were independent prognostic factors for RFS.

CONCLUSION

HIF-1α expression is significantly correlated with initial response to concurrent CRT, and is predictive of RFS for patients with esophageal cancer receiving concurrent CRT.