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S. Pagliaretta



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    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO03.05 - Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome. (ID 2020)

      10:50 - 10:55  |  Author(s): S. Pagliaretta

      • Abstract
      • Presentation
      • Slides

      Background
      Thymomas are uncommon tumors of thymic epithelial cells. Thymomas display significant heterogeneity from morphologic point of view, clinical behaviour, expression of immunohistochemical markers and molecular profiling. Improving our understanding of the molecular biology of thymic malignancies represents a key challenge in the treatment of these rare tumors.

      Methods
      The genomic DNA of 57 consecutive patients (31 females and 26 males; 43 thymomas and 14 thymic carcinomas) submitted to total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes: Hypoxia Inducible Factor-1 alpha (HIF1a: rs2057482T>C, rs1951795A>C, rs2301113C>A, rs10873142C>T, rs11158358G>C, rs12434438G>A, rs11549465C>T, rs11549467G>A), Vascular Endothelial Growth Factor-A (VEGF-A: rs2010963G>C, rs699947A>C), VEGF Receptor 2 (VEGFR-2: rs2305948C>T, rs1870377T>A), VEGFR-3 (rs307826T>C, rs307821C>A), Platelet-Derived Growth Factor-A (PDGFR-A: rs35597368C>T) and Excision Repair Cross-Complementing 1 (ERCC1: rs11615A>G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays.

      Results
      The allele frequency of PDGFR-A rs35597368 T (95.24%) was significantly higher than general population (86%, p=0.012), while the frequency of alleles HIF1-A rs2057482C (76.98%), rs1951795C (68.25%), rs2301113A (68.55%), rs10873142T (68.85%), rs11158358C (74.6%), rs12434438A (65.87%), rs11549465C (83.33%) were significantly lower than those of the control group (90%, 87%, 82%, 87%, 86%, 84%, 92%, respectively, p<0.01). VEGFR-3 rs307821C was significantly higher in thymomas vs. thymic carcinomas (79.5% vs 72%, p=0.0371). The following factors were significantly correlated with a better overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-A rs35597368T/C, HIF1a rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p<0.05).

      Conclusion
      To the best of our knowledge this is the largest monocentric study analyzing the angiogenetic variants in thymic tumors representing a further asset in the definition of high-risk patients after curative resection. The selection tool deriving from this analysis may allow an optimal use of innovative treatment strategies including targeted agents such as sunitinib, sorafenib or pazopanib.

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