These validated pathways are metalloproteinases and regulatory pathways of metalloproteinases, HIF1α induced invasion- and angiogenesis related target genes and the urokinase plasminogen activator system, key pathways involved in invasion, extra cellular matrix remodelling, detachment and angiogenesis, essential steps in the progression to metastatic disease (Tables 4 and 5). This evidence concerns the gene HIF1A and metastatic neoplasm.