Angiogenic switch occurs late in squamous cell carcinomas of human skin

Angiogenesis is a crucial event in carcinogenesis and its onset has been as sociated with premalignant tumour stages. In order to elucidate the signifi cance of angiogenesis in different stages of epithelial skin tumours, we an alysed the vessel density in ten normal skin samples, 14 actinic keratosis (AK), 12 hypertrophic AKs, and in nine early- and 16 late-stage squamous ce ll carcinomas (SCCs). Mean vascular density was quantitated by counting the number of CD 31-immunostained blood Vessels and by morphometric assessment of stained vessel area by computer-assisted image analysis. The results fr om both methods were well correlated. Mean Vascular density was similar in normal dermis and in AK, and only slightly elevated in hypertrophic AKs and early SCC stages (tumour thickness < 2 mm). Only late-stage SCCs infiltrat ing the subcutis exhibited a significant increase in vascularization. Vesse l density was independent of tumour localization, degree of proliferation a nd inflammatory cell infiltration. Furthermore, tumour vascularization was not correlated with the expression of Vascular endothelial growth factor, a major angiogenic factor, as revealed by in situ hybridization and immunohi stochemistry. The restriction of enhanced vascularization to increased tumo ur thickness may be a major reason for the rather low metastatic spread of cutaneous SCCs. (C) 2000 Cancer Research Campaign.