TUMOR ANGIOGENESIS AS A PROGNOSTIC FACTOR IN THICK CUTANEOUS MALIGNANT MELANOMA. A QUANTITATIVE MORPHOLOGIC ANALYSIS

The prognostic value of the extent of neovascularization in cutaneous melanoma is a highly controversial issue. The aim of the current study was to evaluate whether the morphometric analysis of tumor vascularity may be helpful in predicting the clinical outcome of patients with thick cutaneous melanomas. A series of 15 patients with melanoma (>3 mm in thickness) who did not experience disease progression after long-term follow-up (10 years) and 30 matched controls who underwent recurrence and/or metastases were selected for the study. Microvessels were immunohistochemically stained with anti-CD31 antibody. Several parameters, including vessel number, vascular density, vessel area, equivalent circle diameter, perimeter, shape factor, compactness, and the number of vascular ramifications per 100 vessel sections, were quantitatively assessed by a computer-aided semi-automatic image analysis system. Mean vessel area was 341.69 microm2 in cases without progression and 512.55 microm2 in the progressed melanomas (P=0.008, Mann-Whitney U test). The mean equivalent circle diameter was 18.95 microm in non-progressed melanomas and 22.57 microm in progressed melanomas (P=0.009). The mean number of ramifications was 0.8 in cases without progression and 1.9 in the controls (P=0.03). Microvessel count and vascular density were higher in progressed cases (17.37 vs. 11.73 and 28.94/mm2 vs. 19.55/mm2, respectively), but the difference did not reach statistical significance (P=0.06). Our results suggest that neovascularization is a critical event in the progression of thick melanoma. Its prognostic significance is better assessed by quantification of vessel area, equivalent circle diameter, and microvessel branching, whereas microvessel count and vascular density do not provide significant prognostic information.