Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic melanoma patients: correlation with clinical parameters and outcome.

Eur J Cancer 2009 May 20;45(8):1407-14. Epub 2009 Jan 20.

AP-HP, Salpêtrière Hospital, University of Pierre & Marie Curie Paris 6, Laboratory of the Medical Oncology Department, 47 Boulevard de l'Hôpital, 75013 Paris, France.

Purpose: The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that vascular endothelial growth factor-C (VEGF-C), and its receptor VEGFR-3, may play a pivotal role in the promotion of metastasis to regional lymph nodes. This study was designed to detect and evaluate whether the expression of VEGFR-3 or its soluble form plays a role in metastatic malignant melanoma and to determine the relationship with clinicopathological parameters and patients outcome.

Experimental Design: VEGFR-3 expression on melanoma tumour was evaluated by immunohistochemical study. Using a sensitive enzyme-linked immunosorbent assay, sVEGFR-3 was measured in sera of 60 metastatic melanoma patients in comparison with 30 healthy controls.

Results: Immunohistochemical study demonstrated a high expression of VEGFR-3 in melanoma cells. Median level of pre-treatment sVEGFR-3 was significantly higher (p=0.00001) in melanoma patients as compared to healthy donors. No association was noted between VEGFR-3 in situ or in sera and gender, age or LDH level. Median serum VEGFR-3 levels were significantly higher in patients with high tumour burden as compared to those with low tumour burden (p=0.013) as well as in non-responding patients (n=33) as compared to responding ones (n=27). Finally, low level of VEGFR-3 was also related positively to disease free survival (X(2)=3.85, p=0.022).

Conclusion: These results suggest that the expression and high pre-treatment sVEGFR-3 level are significantly correlated to poorer prognosis, and may be promising targets for new therapeutic strategies in melanoma disease.

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http://dx.doi.org/10.1016/j.ejca.2008.12.015DOI Listing
May 2009
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