Abstract
Abstract: :
Purpose: Over–expression of VEGF and over–representation of the 6p region have been previously reported in uveal melanoma (range 0–94% and 31–57%, respectively). The smallest region of gain on 6p includes the physical location of VEGF in 6p21. Currently, there is no available data on the correlation between copy number change in the 6p region and expression of VEGF in uveal melanomas. The aim of the following study is to identify the frequency of copy number alteration in the 6p21 region and its correlation with the expression of VEGF in uveal melanoma. Methods: We studied a total of 82 uveal melanomas. Copy number change in the 6p region was detected by comparative genomic hybridization (CGH) and/or chromogenic in–situ hybridization (CISH). Expression of VEGF protein was estimated by immuno–staining. In a subset of the tumors, VEGF mRNA expression was also studied by quantitative reverse transcriptase PCR (RT–PCR) to confirm the immuno–staining result. Results:We detected moderate to strong immuno–staining for VEGF in 40/82 tumors (49%). Copy number of the 6p21 region was successfully estimated in 31 tumors. Gains of the 6p21 region, ranging from 3–9 copies/tumor cell, were detected in 10 tumors (32%). Over–expression of VEGF was detected in only 2 of these 10 tumors with 6p21 regional gain. There was no statistically significant difference in VEGF expression between tumors with and without gain of 6p21 (p =0.77). Expression of VEGF, detected by quantitative RT–PCR, was in agreement with expression of VEGF protein. VEGF expression was not confined to the tumors and was also detected in the surrounding normal tissue. Conclusions: VEGF is over–expressed in a significant number of uveal melanomas. Of note, VEGF expression can be independent of the copy number of VEGF. Therefore, VEGF over–expression other than structural amplification is probably significant in the pathogenesis of uveal melanomas, and its mechanism must be sought.
Keywords: melanoma • pathobiology • genetics