Expression of angiogenic factors is increased in metastasised renal cell carcinomas

Mahmoud Abbas, Johannes Salem, Angelika Stucki-Koch, Mareike Rickmann, Viktor Grünwald, Thomas Herrmann, Danny Jonigk, Hans Kreipe, Kais Hussein

Clear cell renal cell carcinomas (ccRCC) have aberrant signalling pathways which affect vascular endothelial growth factor and are related to increased tumour angiogenesis. Little is known about other angiogenesis-associated genes in primary tumours and metastases. Quantitative PCR of 45 angiogenesis-associated gene transcripts was performed on formalin-fixed and paraffin-embedded tissues from primary ccRCC (n = 18) and their metastases (n = 17; in 8/17 cases the corresponding primary tumour could be analysed). In metastases, a significant increase was found in the expression of 15 pro-angiogenic (such as prostaglandin-endoperoxide synthase 1) and also anti-angiogenic (such as TIMP metallopeptidase inhibitor 2) factors. Comparison of a primary with its metastasis performed on eight cases showed that even without preceding anti-angiogenic therapy in metastases expression of angiogenic factors is increased. In ccRCC, the effects of anti-angiogenic factors are superimposed by pro-angiogenic factors. Increased expression of angiogenic factors in metastases might be related to development of resistance after anti-angiogenic therapy but might also be an inherent biological characteristic.