"CXCR4-CXCL12 and VEGF correlate to uveal melanoma progression".
Despite improvements in early diagnosis of uveal melanoma, prognosis is still poor due to metastases development. Neoangiogenesis and migration are requisites to metastasis promotion. Cross-talking between CXCR4-CXCL12 axis and the VEGF pathway was shown to favours tumour progression. CXCR4-CXCL12-VEGF expression was evaluated by immunohistochemistry in 53 selected cases of primary uveal melanoma and in liver melanoma metastases. CXCR4 protein was detected in 41.4 per cent cases, CXCL12 in 43.4 per cent cases and VEGF expression in 39.6 per cent cases. A significant correlation was found between CXCR4 and VEGF expression (p=0.011), CXCL12 and both tumour dimension and (p=0.006) and epithelioid-mixed cytotype (p=0.012). The two cases of uveal melanoma liver metastases in our series showed CXCR4 expression, weak immunoreactivity for CXCL12 and absent VEGF immunostaining. These data indicate that CXCR4-CXCL12 axis and its cross-talking with VEGF plays a role in uveal melanoma metastases and may be new prognostic markers in UMM. Moreover, these results suggest that targeted inhibition of CXCR4 could be introduced to control metastasis development in UMM.
Franco
Renato
R
Pathology Department, National Cancer Institute G Pascale, Naples, Italy. renfr@yahoo.com
Botti
Gerardo
G
Mascolo
Massimo
M
Loquercio
Giovanna
G
Liguori
Giuseppina
G
Ilardi
Gennaro
G
Losito
Simona
S
La Mura
Anna
A
Calemma
Rosa
R
Ierano
Caterina
C
Bryce
Jane
J
D'Alterio
Crescenzo
C
Scala
Stefania
S
D054377:Chemokine CXCL12 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014604:Uveal Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D017931:DNA Primers; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A