Article
No correlation between hypoxia-associated markers and oxygenation status in cancers of the uterine cervix
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Published: | March 20, 2006 |
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Tumor hypoxia is a key aspect of the pathophysiology and clinical course of solid malignancies, contributing to tumor progression and therapeutic resistance. Direct oxygenation measurements in the clinical setting using O2 needle electrodes are reliable, but nevertheless invasive, costly and restricted to accessible tumor entities. The transcription factor HIF-1(α) and its target genes CA IX and GLUT-1 are proteins which can be induced in the presence of hypoxia both in vitro and in vivo. Their validity as endogenous markers of tumor hypoxia is currently being investigated, albeit with contradictory results. Since tumor heterogeneity may at least partially account for diverging experimental results, the expression intensities of HIF-1α, CA IX and GLUT-1 have been measured in biopsy specimens of oxygenation measurement tracks of uterine cervix cancers. When both were carried out in identical microareas, no correlation was found between any of these proteins and any of the oxygenation parameters (median pO2, hypoxic fraction ≤ 2.5 mm Hg or hypoxic fraction ≤ 5 mm Hg). Both hypoxic tumors with low marker expression and well-oxygenated tumors with moderate or high marker expression were routinely seen. Concomitant influences of the tumor microenvironment other than hypoxia and activated oncogene signaling pathways may account for these findings. On the basis of these data, a meaningful role of HIF-1α, CA IX and GLUT-1 as endogenous markers of hypoxia appears to be questionable.
Figure 1 [Fig. 1].