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Expression of Vascular Endothelial Growth Factor in Uveal Melanoma Is Independent of 6p21-Region Copy Number

¹ Department of Ophthalmology and ² Clinical Cancer Genetics Program, Human Cancer Genetics Program, Comprehensive Cancer Center; Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio

Requests for reprints: Frederick H. Davidorf, Department of Ophthalmology, Ohio State University, 456 West 10th Avenue, Suite 5B, Columbus, OH 43210. Phone: 614-293-8041; Fax: 614-293-6180; E-mail: Davidorf.1{at}osu.edu.

Purpose: Overexpression of vascular endothelial growth factor (VEGF) and overrepresentation of the 6p region have been reported with a wide variation in uveal melanoma. The aim of the current 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.

Experimental Design: We studied 88 uveal melanomas for copy number change in the 6p region by comparative genomic hybridization and/or chromogenic in situ hybridization. Expression of VEGF protein was estimated by immunohistochemistry. In 15 tumors, VEGF mRNA expression was also studied by quantitative reverse transcription–PCR (RT-PCR) and VEGF splice variants were detected by RT-PCR.

Results: Copy number of the 6p21 region was successfully estimated in 37 tumors. In 10 (27%) of those, overrepresentation of the 6p21 region was detected. There was no statistically significant difference in VEGF expression between tumors with and without gain of 6p21 (P = 0.82). VEGF expression was not confined to the tumors and was also detected in the surrounding normal tissue. Expression of VEGF, detected by quantitative RT-PCR, was concordant with expression of VEGF protein. Different VEGF isoforms were expressed in different tumors with no obvious correlation with disease status.

Conclusion: VEGF is overexpressed in a significant number of uveal melanomas. It should be noted that VEGF is not a candidate oncogene in uveal melanoma with 6p gain/amplification. VEGF overexpression other than structural amplification is probably significant in the pathogenesis of uveal melanomas, and its mechanism must be sought.

Key Words: Molecular cytogenetics • comparative genomic hybridization (CGH) • Chromogenic in situ hybridization (CISH) • VEGF splice variants

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