The role of angiogenetic single-nucleotide polymorphisms in thymic malignancies and thymic benign lesions.

Abstract

BackgroundWe previously showed that selected single-nucleotide-polymorphisms (SNPs) of genes involved in angiogenesis influence the aggressiveness of thymic epithelial tumors (TETs). This study analyzes their role in TETs and in thymic benign lesions, in order to investigate potential correlation with risk and outcome.MethodsGenomic DNA was extracted from paraffin-embedded tissue of 92 patients, undergoing surgery at our Institution. We investigated by Real-Time PCR the SNPs of the following genes: platelet-derived growth factor receptor-α (PDGFRα), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor-2 and 3 (VEGF-2, VEGFR-3), excision repair cross-complementation group-1 (ERCC1).ResultsFifty-seven TETs and 35 thymic benign lesions were included into the study. Frequency of SNPs was as follows: rs2057482 C, rs11158358 C and rs11549465 C polymorphisms of HIF1-a: thymomas < general population (P=0.008, P=0.007, and P=0.044 respectively). HIF1-a alleles: general population > study groups, rs1951795C SNP (P=0.026 for benign lesions and P=0.0007 for thymomas), rs10873142T SNP (P=0.008 and P=0.001 respectively), rs12434438 A SNP (P=0.034 and P=0.0007) and rs2301113A SNP (P=0.027 and P=0.010). rs699947C polymorphism of VEGF-A: benign lesions > general population (P=0.012).ConclusionsThis is the first study investigating the angiogenetic polymorphisms in thymic benign lesions and TETs. SNPs analysis may represent a further asset in identification of patients who could benefit from anti-angiogenetic therapy.