title: Survivin protein expression and hypoxia in advanced cervical carcinoma of patients treated by radiotherapy.
abstract: BACKGROUND
  Survivin is strongly overexpressed in the vast majority of cancers. Initial investigations suggest a role for Survivin in radiation resistance. In this study, we investigate the effect of Survivin expression on clinical outcome and its relationship to tumor oxygenation parameters, expression of Hif-1alpha and anemia in patients with advanced cervical cancers treated with radiotherapy.
  
  
  METHODS
  Biopsies of 44 patients with cervical cancers (Stage IIB: n=9; Stage IIIB: n=31; Stage IVA: n=4) treated with radiotherapy were assessed by immunochemistry for expression of Survivin. Relation of Survivin to pretreatment tumor oxygenation parameters (HF5, pO(2)), hemoglobin (hb) level, Hif-1alpha expression and clinical parameters were investigated.
  
  
  RESULTS
  Survivin expression was detected in all tumors of the 44 patients. Seven showed a strong expression and 37 have moderate Survivin expression. Patients whose tumors showed moderate Survivin expression had a 5-year overall survival of 66%. However, only one of the seven patients with strong Survivin expression was alive 45 months after treatment. In a Cox regression analysis, Survivin expression was correlated to poor overall survival (p=0.02, RR=3.3). There was no relationship between Survivin expression and pO(2) or HF5, but rather an inverse correlation with hemoglobin level (p=0.04). Furthermore, for six of the seven tumors with a high Survivin expression, Hif-1alpha was detected.
  
  
  CONCLUSIONS
  Survivin protein expression is linked with anemia and prognosis in advanced cervical carcinoma of patients treated by radiotherapy.
authors.affiliation: Department of Radiotherapy, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Halle, Vossstr. 1, D-06097 Halle/Saale, Germany. matthias.bache@medizin.uni-halle.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.forename: Daniel
authors.initials: D
authors.lastname: Holzapfel
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Holzhausen
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dunst
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hänsgen
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011379:Prognosis; D011446:Prospective Studies; D000077022:Survivin; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: C107489:BIRC5 protein, human; C497442:HIF1A protein, human; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D010100:Oxygen