title: Clinical significance of HIF-1alpha expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Radiology, University of the Ryukyus School of Medicine, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. kogawa@med.u-ryukyu.ac.jp
authors: Kazuhiko
authors: K
authors: Ogawa
authors: Itaru
authors: I
authors: Chiba
authors: Takamitsu
authors: T
authors: Morioka
authors: Hideaki
authors: H
authors: Shimoji
authors: Wakana
authors: W
authors: Tamaki
authors: Reika
authors: R
authors: Takamatsu
authors: Tadashi
authors: T
authors: Nishimaki
authors: Naoki
authors: N
authors: Yoshimi
authors: Sadayuki
authors: S
authors: Murayama
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D005472:Fluorouracil