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


METHODS
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).


CONCLUSIONS
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.
Mouawad
Roger
R
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.
Spano
Jean-Philippe
JP
Comperat
Eva
E
Capron
Frederique
F
Khayat
David
D
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D016022:Case-Control Studies; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000097:blood / Q000737:chemistry* / Q000401:mortality; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012878:Skin Neoplasms / Q000097:blood / Q000737:chemistry* / Q000401:mortality; D015996:Survival Rate; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis* / Q000097:blood; D055815:Young Adult
D014408:Biomarkers, Tumor; D040321:Vascular Endothelial Growth Factor Receptor-3