Clinical markers and driving mechanisms in melanoma progression: VEGF-C, RhoC, c-Ski/SnoN and EGFR.

This research project aimed at evaluating the clinical and prognostic value of different molecules involved in signalling transduction pathways involved in melanoma progression. Vascular endothelial growth factor-C or VEGF-C induces lymphangiogenesis. This study showed high VEGF-C expression to be associated with the presence of a positive sentinel lymph node. The presence of VEGF-C expression in melanoma cells was associated with reduced disease free and overall survival. RhoC is important in the organization of the actin filamental system. We observed RhoC mRNA and protein expression to be upregulated in a highly metastatic melanoma cell line (DX3aza), whereas only low expression levels were found in a melanoma cell line with low proliferative and invasive capacity (MeWo). RhoC immunoreactivity in melanoma tissue was associated with high Breslow tumour thickness and the presence of ulceration. C-Ski and SnoN have been identified as negative regulators in the TGF-beta pathway. We found a significant association between the presence of nuclear c-Ski and thicker, ulcerated melanomas. SnoN expression was associated with the presence of ulceration and a positive sentinel lymph node. Epidermal Growth Factor Receptor (EGFR) expression has been associated with tumour progression and poor outcome in a variety of solid tumours, EGFR immunoreactivity was more frequently present in patients with a positive sentinel lymph node. EGFR gene amplification was not observed; however, the presence of polysomy was associated with higher Breslow tumour thickness. Treating BLM melanoma cells with different concentrations of cetuximab reduced the invasive capacity of the melanoma cells, without impact on cell viability and growth.