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Investigative Report

Vascular Endothelial Growth Factor Receptor-3 Expression Predicts Sentinel Node Status in Primary Cutaneous Melanoma

Ferdinand Toberer, Holger A. Haenssle, Martin Laimer, Monika Heinzel-Gutenbrunner, Alexander Enk, Wolfgang Hartschuh, Peter Helmbold, Heinz Kutzner
DOI: 10.2340/00015555-3588

Preview of fully accepted paper, still not published in any volume

Abstract

This study analysed the expression of vascular endothelial growth factor-A (VEGF), VEGFR-2, and VEGFR-3 in primary cutaneous melanomas with positive and negative sentinel node status (SLN) (a total of 58 specimens divided into 2 groups of 29 for each status). The specimens were collected from the pathological archive of the department of Dermatology, Venereology and Allergology of the University Medical Center Heidelberg. A quantification score was developed for protein expression, by considering the percentage of positive melanoma cells (0: 0%, 1: up to 1%, 2: 2–10%, 3: 11–50%, and 4: > 50%) in relation to the intensity of staining (0: negative, 1: low, 2: medium, 3: strong). Tumoural VEGFR-3 expression (mean ± standard deviation) in SLN+ tumours (9.62 ± 3.09) was significantly stronger than in SLN– tumours (6.13 ± 3.87; p < 0.001). A binary logistic regression model proved VEGFR-3 expression and tumour thickness to be significant independent predictors of SLN. These data provide evidence that VEGFR-3 expression may play a critical role in the pathogenesis of malignant melanoma and that its investigation may help to improve the selection of patients with primary cutaneous melanoma for sentinel node biopsy.

Significance

The aim of this study was to analyse the expression of proteins that contribute to angiogenesis in primary cutaneous melanoma. Expression of vascular endothelial growth factor-A (VEGF), VEGFR-2, and VEGFR-3 were investigated by immunohistochemistry in a matched cohort of primary cutaneous melanomas with positive and negative sentinel lymph node status (SLN). The results reveal differences in the expression of VEGF and VEGFR-3 in tumours with positive and negative SLN, and that expression of VEGFR-3 is an independent predictor of SLN. Further studies are needed to confirm these results and show whether they may have therapeutic implications.

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