Expression of vascular endothelial growth factor in early cutaneous melanocytic lesion progression

Abstract

BACKGROUND: A considerable body of evidence supports the concept that a significant number of cutaneous malignant melanomas progress through a precursor lesion or dysplastic melanocytic nevi (DN). Tumor angiogenesis likely plays a critical role in early development of melanoma, and intermediate biomarkers of angiogenesis could be useful as chemoprevention and prognostic markers. METHODS: Markers of angiogenesis that included expression of the vascular endothelial growth factor A (VEGF-A) and microvessel density counts (MVD) were evaluated in 13 prospectively collected benign nevi (BN) and 19 DN from 16 individuals and in a comparison group of 17 primary melanomas (16 archival samples and 1 prospective melanoma). RESULTS: VEGF expression in melanocytic cells (mean+/-standard error [SE]) was low or absent in BN (3.4+/-1.4), increased significantly in DN (41.0+/-10.1; P=.0003 for BN vs DN), and increased further in primary melanoma (119.9+/-28.3; P = .06 for DN vs melanoma). MVD using CD31 (mean+/-SE [percentage x intensity]) followed a similar pattern with similarity between BN (2.6+/-0.7; N=13) and DN (2.2+/-0.8; N=19; P=.4 for BN vs DN), whereas primary melanomas were significantly higher (39.4+/-6.4; N=17; P=.0001 for BN or DN vs melanoma). CONCLUSIONS: In a prospective setting, the current data suggested that increased VEGF-A expression in DN may be a good indicator of preneoplastic change in melanocytic lesions with the potential for improving the understanding and prevention of the transformation of DN to melanoma.