Vascular endothelial growth factor-A (VEGF-A), expressed in 26–83% of patients with CUP, is a well-known signalling protein that binds to stimulatory cell-surface receptors expressed by vascular endothelial cells.57,76,83,84 Its expression does not have any prognostic implications, although previously published data showed that tumour microvessel density was an adverse prognostic factor in patients with liver metastases of unknown primary.82 VEGF can be sequestered in the extracellular matrix in latent forms and later released and activated by extracellular matrix-degrading proteases. Here, VEGFA is linked to neoplasm.