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Inhibitory isoforms of VEGF in uveal melanoma
Author(s) -
COUPLAND SE
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.4265.x
Subject(s) - angiogenesis , melanoma , monosomy , cancer research , metastasis , immunohistochemistry , medicine , bevacizumab , vascular endothelial growth factor , pathology , cancer , biology , vegf receptors , chromosome , chemotherapy , karyotype , genetics , gene
Purpose Uveal melanoma (UM) affects around 600 new patients in the UK each year with half of these being treated at the Liverpool Ocular Oncology Centre. UM is an unusual tumour in that gross chromosomal abnormalities are strongly associated with metastatic spread, especially monosomy 3 & chromosome 8q gain. Mechanisms that underlie this remain unclear. Methods Angiogenesis is a requirement for tumour survival & metastasis. Vascular Endothelial Growth Factor (VEGF) is known to be the most potent stimulator of angiogenesis and increased expression of VEGF‐A is linked to enhanced metastatic potential in UM. Treatment with bevacizumab (anti‐VEGF therapy) suppresses hepatic micrometastasis of ocular melanoma cells in animal models. However, VEGF‐A data in UM are variable, with some studies demonstrating no correlation between VEGF‐A expression and metastasis or survival. Results VEGF‐A was accepted as a single pro‐angiogenic family of protein isoforms generated from alternatively spliced mRNA (VEGF189, VEGF165 etc). However, recently a family of sister isoforms named VEGFxxxb, where xxx is the amino acid number and b a different six C‐terminus amino acids (VEGF189b, VEGF165b) has been discovered. The VEGFxxxb variants are exactly the same size as pro‐angiogenic VEGFxxx, yet are antiangiogenic. VEGF165b is down‐regulated in primary cutaneous melanoma that later metastasises, and over‐expression of VEGFxxxb isoforms confers a protective anti‐tumour effect. Conclusion Immunohistochemical expression of pro‐ and anti‐angiogenic VEGF‐A in 19 UM was assessed using pan‐VEGF‐A and VEGF165b specific antibodies. A statistically significant reduction in expression of VEGF165b was observed in monosomy 3 UM (non‐parametric ANOVA; p<0.05). This suggests that VEGF165b expression may be a useful predictor of UM metastasis.