Prognostic value of HIF-1α expression during fractionated irradiation.
OBJECTIVE
Hypoxia and reoxygenation are important determinants of outcome after radiotherapy. HIF-1α is a key molecule involved in cellular response to hypoxia. HIF-1α expression levels have been shown to change after irradiation. The objective of the present study was to explore the prognostic value of HIF-1α expression during fractionated irradiation.


METHODS
Six human squamous cell carcinoma models xenografted in nude mice were analysed. Tumours were excised after 3, 5 and 10 fractions. HIF-1α expression was quantified by western blot. For comparative analysis, previously published data on local tumour control data and pimonidazole hypoxic fraction was used.


RESULTS
HIF-1α expression in untreated tumours exhibited intertumoural heterogeneity and did not correlate with pimonidazole hypoxic fraction. During fractionated irradiation the majority of tumour models exhibited a decrease in HIF-1α expression, whereas in UT-SCC-5 no change was observed. Neither kinetics nor expression levels during fractionated irradiation correlated with local tumour control.


CONCLUSIONS
Our data do not support the use of HIF-1α determined during treatment as a biomarker to predict outcome after fractionated irradiation.
Dept. of Radiation Oncology/ OncoRay National Center for Radiation Research, Medical Faculty and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
L
L
Helbig
A
A
Yaromina
S N
SN
Sriramareddy
S
S
Böke
L
L
Koi
H D
HD
Thames
M
M
Baumann
D
D
Zips
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000528:radiation effects; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D005260:Female; D015870:Gene Expression / Q000528:radiation effects*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009593:Nitroimidazoles / Q000494:pharmacology; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D013223:Statistics as Topic; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole