Impact and Prognostic Role of Single-Neucleotide Polymorphisms (snps) in Thymic Lesions

Introduction: The thymus may present a large spectrum of morphological benign proliferative changes as thymic hyperplasia and malignant neoplasms, as thymoma and thymic carcinoma (Thymic Epitelial Tumors, TETs), that display significant heterogeneity. Angiogenesis has been highlighted as a needful component in development of thymic tumors. Therefore, the improvement of our knowledge of the molecular biology of thymic disorders represents a key challenge in the treatment of these rare diseases. Patients and methods: The genomic DNA of 92 consecutive patients, undergone surgery or biopsy was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes involved in the angiogenesis mechanism: Platelet-Derived Growth Factor alpha (PDGFR-&agr;: rs35597368T > C), Hypoxia Inducible Factor-1 alpha (HIF1-&agr;: rs2057482C > T, rs1951795C > A, rs2301113A > C, rs10873142T > C, rs11158358C > G, rs12434438A > G, rs11549465C > T, rs11549467G > A), Vascular Endothelial Growth Factor-A (VEGF-A: rs2010963G > C, rs699947C > A). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Results: Ninty-two patients were included into the study, 57 females and 35 males. Eighty-seven patients underwent surgery (52 for thymomas or thymic carcinoma and 35 for thymic benign lesions), while 5 patients showed metastatic or locally advanced disease (3 thymomas and 2 thymic carcinomas). The frequency of rs35597368T allele of PDGFR-a was higher in TETs compared to general population (p = 0.037). The frequency of rs2057482C and rs11158358 C polymorphisms of HIF1-a resulted lower in TETs than in general population (p = 0.011 and p = 0.012, respectively). The frequency of 4 HIF1-a alleles was higher in general population than study groups: rs1951795C SNP (p = 0.026 for the benign lesions group and p = 0.002 for malignancy group, respectively), rs10873142T SNP (p = 0.008 and p = 0.003 respectively), rs12434438 A SNP (p = 0.034 and p = 0.002) and rs2301113A SNP (p = 0.027 and p = 0.022). The frequency of rs699947C polymorphism of VEGF-A was higher in patients with benign lesion in comparison with general population (p = 0.012). Conclusions: To the best of our knowledge this is the largest monocentric study analyzing the angiogenetic variants in thymic benign lesions and thymic malignancies. The selection tool deriving from this analysis may allow an optimal use of innovative treatment strategies including targeted agents.