[Frontiers in Bioscience E2, 13-21, January 1, 2010]

"CXCR4-CXCL12 and VEGF correlate to uveal melanoma progression"

Renato Franco1, Gerardo Botti1, Massimo Mascolo2, Giovanna Loquercio1, Giuseppina Liguori1, Gennaro Ilardi2, Simona Losito1, Anna La Mura3, Rosa Calemma4, Caterina Ieranò 4, Jane Bryce5, Crescenzo D'Alterio4, Stefania Scala4

1Pathology Department, National Cancer Institute ' G. Pascale', Naples, Italy, 2Biomorphological and Functional Sciences Department, Pathology Section, "Federico II" University, Naples, Italy, 3Pathology Unit, "A. Cardarelli" Hospital, Naples, Italy,4Immunology Unit, National Cancer Institute ' G. Pascale', Naples, Italy, 5Clinical Trials Unit, National Cancer Institute ' G. Pascale', Naples, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods 3.1 .Histology
3.2. Immunohistochemistry
3.3. RNA isolation and reverse transcriptase-PCR
3.4. Reverse transcriptase-PCNA
3.5. Statistical analysis
4. Results
4.1. Patient and tumour characteristics
4.2. CXCR4, CXCL12 and VEGF expression in uveal melanoma: pattern of expression
4.3. Expression of CXCL12 correlated with melanoma dimension and cytotype
4.4. CXCR4, VEGF and SDF1/CXCL12 expression: correlation to outcome
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

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% cases, CXCL12 in 43.4% cases and VEGF expression in 39.6% 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.