Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in human malignant melanoma and their relation to angiogenesis

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Abstract

Background

Angiogenesis is the major and key factor for growth and invasion of tumours, including malignant melanoma (MM), but the factors that contribute to tumour angiogenesis are still unclear.

Objective

To study expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in human MM and their relation to angiogenesis. To investigate the correlation between eNOS and VEGF and the role of nitric oxide (NO) generated by eNOS in the process of mediating angiogenesis by VEGF.

Methods

Tissue sections from 31 patients with MM were examined using immunohistochemistry and morphological quantitative analysis for protein expression of eNOS and VEGF. Microvessel density (MVD) was counted in endothelial cells in immunostained by anti-FVIII:RAg antibody.

Results

Positive eNOS and VEGF immunostaining were observed in 77.4% and 83.9% of MM lesions, respectively, whereas pigmented naevi never expessed eNOS and VEGF. A positive correlation between eNOS and VEGF in MM was observed. Expression of eNOS and VEGF was positively correlated with MVD expression in MM, and MVD expression in MM was stronger than in pigmented naevi. Expression of eNOS and VEGF was not correlated with lymph node metastasis.

Conclusions

On the basis of the current data showing that malignant melanocytic tumours displayed strong VEGF and eNOS expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF and eNOS, such expression may be used as a discriminating factor to distinguish malignant melanoma from pigmented naevi. Expression of eNOS and VEGF may contribute to angiogenesis of MM, eNOS probably plays an important role in mediating VEGF-induced angiogenesis.

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