Comparison of hypoxia-inducible factor-1α expression before and after transcatheter arterial embolization in rabbit VX2 liver tumors

PURPOSE: To test the hypothesis that transcatheter arterial embolization (TAE) induces expression of hypoxiainducible factor-1 alpha (HIF-1 alpha) within the same rabbit VX2 liver tumor. MATERIALS AND METHODS: Seven VX2 tumors were grown in the livers of five New Zealand white rabbits. Ultrasonography-guided biopsy was performed before and 10 minutes after TAE in all tumors. Pre- and post-TAE tumor biopsy specimens along with post-TAE whole liver tumor sections were stained with HIF-1 alpha antibody and analyzed for percentage of HIF-1 alpha-positive nuclei by using a spectral unmixing system mounted on a high-powered microscope. Statistical data comparisons were performed with the Wilcoxon signed-rank test (alpha = 0.05). RESULTS: TAE of liver tumors resulted in a statistically significant increase in the mean percentage of HIF-1 alpha expression. The mean percentage of HIF-1 alpha-positive stained nuclei increased from 23% +/- 3.5 in pre-TAE biopsy specimens to 41% +/- 8.7 in post-TAE biopsy specimens (P < .02). The increase was even more significant when the mean percentage of HIF-1 alpha-positive stained nuclei from the same pre-TAE biopsy specimens was compared with sections from post-TAE whole tumor specimens (60% +/- 8.9, P < .02). CONCLUSIONS: The results of this study revealed that hypoxia caused by TAE of VX2 liver tumors activates HIF-1 alpha, a transcription factor that in turn regulates other pro-angiogenic factors.