Stochastic relationship between the growth fraction and vascularity of thin malignant melanomas

Tumour vascularity has been proposed as a prognostic indicator for a number of solid tumours. In these respects the situation is unclear for cutaneous malignant melanoma (MM). The small number of MM cases studied to date have indicated controversial preliminary conclusions. Hence, tumour thickness remains currently the most reliable prognostic factor for MM. This variable has been shown in previous work to be correlated with both the S-phase fraction and the growth fraction of the MM cells. We studied the relationship between vascularity and growth fraction of 100 thin (< 1 mm) cutaneous MM using immunohistochemistry (Ulex europaeus agglutinin-type 1 (UEA-1) and MIB-1 antibody (Ki-67)) and computerised image analysis. A stochastic relationship was found between intra- and peritumoral vascularity, and between Ki-67 and UEA-1 measures. Approximately 20-40% of PC-MM showing a high Ki-67-positive growth fraction (breakpoint: 30/0.4 mm2) were characterised by a prominent vascularity at the boundary of the neoplasm. In these cases, vessels often exhibited either heterogeneous lumen sizes or a uniform prominent dilated network. The present study shows that the angiogenic phenotype of MM occurs as a stochastic event during neoplastic progression. Its expression is not mandatory for reaching high values in MM growth fraction. It can be hypothesised that the absence of a link between proliferation and vascularity might account for the unusual outcome of some cutaneous MM, including the dormant growth-stunted type and the metastasising thin MM.