Tumor specific activation of the VEGF/KDR angiogenic pathway in a subset of locally advanced squamous cell head and neck carcinomas

Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and flk- 1(KDR), constitute an important angiogenic pathway which, under hypoxic con ditions, is up-regulated in many solid tumours. We used the monoclonal anti body 11B5, specific for recognizing VEGF expression and the `VEGF/flk-1(KDR ) complex' on tumour endothelium, to assess free VEGF protein expression an d VEGF/receptor activated microvessel density (aMVD) in a series of 104 ino perable locally advanced squamous cell carcinomas of the head and neck, tre ated with chemo-radiotherapy. High VEGF expression in cancer cells was stro ngly associated with high VEGF/receptor expression in the vasculature. The high VEGF expression and the aMVD were not associated with the standard mic rovessel density (sMVD), as assessed with the monoclonal antibody anti-CD31 and, were not detected in normal tissue. An increased sMVD, however, was s ignificantly related with the expression thymidine phosphorylase (TP), and also with the nuclear accumulation of the oncoprotein p53, but neither p53 nor TP was associated with VEGF expression by cancer cells or VEGF/receptor complex aMVD. In 35% of cancer cases examined, more than 20% of the microv essels assessed with anti-CD31 also expressed the VEGF/KDR complex. The vas culature of the normal head and neck mucosa did not express the VEGF/KDR co mplex. There was no association between VEGF expression or VEGF/receptor co mplex aMVD and response to chemo-radiotherapy or patient's survival. It is concluded that activation of the angiogenic pathway VEGF/flk-1(KDR) is tumo r specific in a subgroup of locally advanced squamous cell carcinomas of th e head and neck. Selective destruction of this type of vasculature, using i mmunoconjugates directed against the VEGF/receptor complex, may prove thera peutically useful for patients with a high tumoral VEGF/flk-1(KDR) activate d microvessel fraction.