Endogenous hypoxia markers in locally advanced cancers of the uterine cervix: reality or wishful thinking?
BACKGROUND
Tumor hypoxia is considered to be relevant for several aspects of tumor pathophysiology, for acquired treatment resistance, and tumor progression (e. g., in cancers of the uterine cervix). Therefore, there is a demand for simple and universally applicable methods allowing the estimation of oxygenation status in patient material obtained during pretherapeutic diagnostic procedures (biopsies) or surgical treatment. Protein members of the transcriptional response to hypoxia expressed in tumor tissue, e. g., hypoxia-inducible factor-1alpha (HIF-1alpha), glucose transporter-1 (GLUT-1) and carbonic anhydrase IX (CA IX) are currently being discussed as "endogenous hypoxia markers".


METHODS
The (hypothetic) suitability of different markers for the assessment of the oxygenation status is reviewed on the basis of current knowledge.


RESULTS
Data from studies investigating the suitability of different markers are conflicting. Although a robust induction of HIF-1alpha, GLUT-1 and CA IX by hypoxia has been demonstrated in vitro, this reaction is modulated both by confounding factors of the tumor microenvironment and intrinsic traits of malignant cells in vivo.


CONCLUSIONS
On the basis of the available data, the suitability of "endogenous hypoxia markers" for the estimation of the oxygenation status of advanced cervix cancers seems questionable.
Mayer
Arnulf
A
Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany. arnmayer@uni-mainz.de
Höckel
Michael
M
Vaupel
Peter
P
D015415:Biomarkers; D001706:Biopsy; D002256:Carbonic Anhydrases / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D010100:Oxygen / Q000378:metabolism*; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002256:Carbonic Anhydrases; D010100:Oxygen