Survivin protein expression and hypoxia in advanced cervical carcinoma of patients treated by radiotherapy.
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.
Bache
Matthias
M
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
Holzapfel
Daniel
D
Kappler
Matthias
M
Holzhausen
Hans-Jürgen
HJ
Taubert
Helge
H
Dunst
Jürgen
J
Hänsgen
Gabriele
G
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*
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