Significant correlation of hypoxia-inducible factor-1alpha with treatment outcome in cervical cancer treated with radical radiotherapy.
OBJECTIVE
In the early stages of cervical cancer treated with surgery alone, hypoxia-inducible factor-1alpha (hif-1alpha) expression is prognostic for overall survival. Because hypoxia plays an important role in radiation resistance, we investigated hif-1alpha expression in cervical cancer treated with local radical radiotherapy (RT).


METHODS
Between 1990 and 1998, 91 patients with squamous cell or adenocarcinoma of the uterine cervix were treated with external beam RT with and without brachytherapy. Biopsies from 78 patients were available for immunohistochemistry. The impact of the immunoreactivity of hif-1alpha in regard to survival end points was determined by univariate and multivariate analyses. Correlations with clinicopathologic characteristics were determined by cross-tabulations.


RESULTS
Hif-1alpha was expressed in 73 (94%) of 78 patients. It was closely linked to the pretreatment hemoglobin level (p = 0.04, r = -0.22, Spearman correlation test). The Kaplan-Meier curves showed a significantly shorter local progression-free survival (p = 0.04, log-rank) and overall survival (p = 0.01, log-rank) and a trend for shorter disease-free survival (p = 0.15) for patients with increased hif-1alpha expression. The multivariate analyses revealed hif-1alpha expression to be an independent factor for overall survival (p = 0.02).


CONCLUSIONS
Hif-1alpha is expressed in the vast majority of patients with advanced cervical cancer and had a prognostic significance. A weak but significant correlation was noted with pretreatment hemoglobin level.
Department of Radiation Oncology, University of Berne, Bern, Switzerland.
Philipp
P
Burri
Valentin
V
Djonov
Daniel M
DM
Aebersold
Katja
K
Lindel
Ueli
U
Studer
Hans J
HJ
Altermatt
Luca
L
Mazzucchelli
Richard H
RH
Greiner
Günther
G
Gruber
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D014157:Transcription Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors