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VEGFA gene amplification associated with poor prognosis in osteosarcoma
Yang J. Cancer. 2011;doi:10.1002/cncr.26116.
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Results from an analysis of tissue sections from 58 patients with osteosarcoma show that the vascular endothelial growth factor pathway genes, including VEGFA, are amplified in osteosarcoma.
VEGFA amplification is a poor prognostic factor for tumor-free survival, as well as an important mechanism for elevated VEGFA protein expression.
Researchers collected clinicopathologic data and formalin-fixed, paraffin-embedded tissue sections from 58 patients treated for primary, conventional, central osteosarcoma at the Tianjin Medical University Cancer Institute and Hospital in Tianjin, China. To identify the altered pathways, researchers analyzed recurrent amplified and deleted genes using the Kyoto Encyclopedia of Genes and Genomes.
Researchers identified 33 key pathways with multiple component genes altered at the chromosome level. These pathways included the VEGF signaling, mammalian target of rapamycin, cellular adhesion molecule, adherens junction, Wnt and hedgehog signaling pathways. The VEGF pathway was most frequent, with 13 amplified genes, including VEGFA.
Abundant expression of VEGFA was noted in 74.1% of patients with osteosarcoma. Further analysis showed that VEGFA gene amplification had a strong correlation with abundant VEGFA protein expression, which researchers said suggests that VEGFA gene amplification contributes to the elevated expression of VEGFA and vascular features in osteosarcoma, and poorer survival. A survival analysis on patients with VEGFA gene amplification showed that DFS rates were lower in this group.
Researchers then stratified patients into low and high VEGFA groups. Those in the high group had both VEGFA gene amplification and positive VEGFA protein expression. Kaplan-Meier analysis showed that tumor-free survival rates were worse for patients in the high VEGFA group (P=.037).
Yang and colleagues said the pattern of overall copy number alterations from their microarray-based comparative genomic hybridization dataset was surprisingly similar to that of patients evaluated in Canada and Norway, which suggests that issues of small sample size frequently associated with most cancer types may not be so serious for osteosarcoma.
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