Circulating vascular endothelial growth factor in cutaneous malignant melanoma

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Abstract
Background Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). Objectives To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. Methods In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002–04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean ± SD follow-up 13·4 ± 0·8 months). Data were compared with the extent of the disease and the clinical course. Results A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL−1 was found in 20 (sensitivity 57·1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34·5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. Conclusions Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.

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