Prognostic impact of HIF-1alpha expression in patients with definitive radiotherapy for cervical cancer.
OBJECTIVE
To investigate the relationship between the hypoxia-inducible factor-(HIF-)1alpha expression in tumor tissue, tumor oxygenation and hemoglobin levels in patients with advanced cervical cancers prior to radiotherapy and the effect on clinical outcome.


METHODS
The investigation included 44 patients who underwent definitive radiotherapy for advanced cervical cancers between May 1995 and March 1999. Tumor biopsies were taken prior to treatment, and HIF-1alpha expression was determined by immunohistochemistry. In the same tumor area, tumor tissue oxygenation (pO2) was measured using the Eppendorf device.


RESULTS
The 5-year cancer-specific survival of all patients was 60%. Twelve of 44 tumor specimens were HIF-1alpha-negative with a significantly better 5-year survival (92 +/- 8%) versus 32 patients who were HIF-1alpha-positive (45 +/- 10%; p < 0.02). There was no correlation between HIF-1alpha expression and tumor oxygenation (p = 0.57 both for pO2 median and hypoxic fraction < 5 mmHg vs. HIF-1alpha expression). However, patients with hemoglobin levels < 11 g/dl showed elevated HIF-1alpha expression compared to patients with hemoglobin levels > 12.5 g/dl (p = 0.04). Furthermore, HIF-1alpha correlated with vascular endothelial growth factor expression (p = 0.002). In a multivariate Cox regression model, HIF-1alpha expression (relative risk [RR] = 7.5; p = 0.05) revealed an increased risk of tumor-related death.


CONCLUSIONS
The study indicates, that endogenous tumor markers such as HIF-1alpha may serve as prognostic markers of clinical outcome concerning cervical cancer after primary radiotherapy.
Dellas
Kathrin
K
Department of Radiotherapy, Martin Luther University of Halle-Wittenberg, Germany.
Bache
Matthias
M
Pigorsch
Steffi U
SU
Taubert
Helge
H
Kappler
Matthias
M
Holzapfel
Daniel
D
Zorn
Ester
E
Holzhausen
Hans-Juergen
HJ
Haensgen
Gabriele
G
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001706:Biopsy; D001918:Brachytherapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002584:Cervix Uteri / Q000473:pathology; D003627:Data Interpretation, Statistical; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010100:Oxygen / Q000378:metabolism; D010315:Particle Accelerators; D011048:Polarography; D011379:Prognosis; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen