Abstract 2220: Impact of single-nucleotide polymorphisms (SNPs) on thymic hyperplasia and tumors outcome
Authors: Berardi Rossana , Pagliaretta Silvia , Brunelli Alessandro , Paolucci Vittorio , Goteri Gaia , Refai Majed , Pompili Cecilia , Savini Agnese , Marcantognini Giulia , Torniai Mariangela , Tiberi Michela , Ferrini Consuelo , Morgese Francesca , Caramanti Miriam , Rinaldi Silvia , Onofri Azzurra , Zizzi Antonio , Mazzanti Paola , Cascinu Stefano 
Published: May 2015

Background: Thymic Hyperplasia refers to an enlargement of the thymus, while thymomas display significant heterogeneity from morphologic point of view, clinical behaviour, expression of immunohistochemical markers and molecular profiling. Therefore improving our understanding of the molecular biology of thymic disorders represents a key challenge in the treatment of these rare diseases.

Methods:

The genomic DNA of 93 consecutive patients undergoing total thymectomy at our Institution was extracted from paraffin-embedded tissue.

We selected the following SNPs: Hypoxia Inducible Factor-1 alpha (HIF1a: rs2057482T&gt;C, rs1951795A&gt;C, rs2301113C&gt;A, rs10873142C&gt;T, rs11158358G&gt;C, rs12434438G&gt;A, rs11549465C&gt;T, rs11549467G&gt;A), Vascular Endothelial Growth Factor-A (VEGF-A: rs2010963G&gt;C, rs699947A&gt;C), VEGF Receptor 2 (VEGFR-2: rs2305948C&gt;T, rs1870377T&gt;A), VEGFR-3 (rs307826T&gt;C, rs307821C&gt;A), Platelet-Derived Growth Factor-A (PDGFR-A: rs35597368C&gt;T).

Gene polymorphisms were determined by Real-Time PCR using TaqMan assays.

Results:

93 patients were included into the study, 58 females and 35 males.

The patients underwent surgery: 43 for thymomas, 14 for thymic carcinomas, 36 for thymic hyperplasia.

The frequency of PDGFRa rs35597368T (95.24%) was significantly higher in thymic malignancies if compared with data available for population (86%, p=0.012), thus suggesting that it may represent a risk factor for this type of disease. On the other hand, the frequency of several HIF-1a polymorphisms (rs2057482C, rs11549465C, rs1951795C, rs2301113A, rs10873142T, rs11158358C, rs12434438A) resulted lower in our study than in the general population (p&lt;0.05). In particular, frequencies of HIF1a rs1951795C, rs2301113A, rs12434438A were significantly lower in thymic malignancy than in thymic hyperplasia and moreover these were lower than population, according to available literature data on other types of tumors, suggesting a protective role.

Furthermore, VEGFR3 rs307821C polymorphism was higher in thymoma than in thymic carcinoma (79.5% vs 72%, p=0.0371), and therefore it seems to be related to a lower grade of malignancy.

Finally, 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 (p&lt;0.05).

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

Citation Format: Rossana Berardi, Silvia Pagliaretta, Alessandro Brunelli, Vittorio Paolucci, Gaia Goteri, Majed Refai, Cecilia Pompili, Agnese Savini, Giulia Marcantognini, Mariangela Torniai, Michela Tiberi, Consuelo Ferrini, Francesca Morgese, Miriam Caramanti, Silvia Rinaldi, Azzurra Onofri, Antonio Zizzi, Paola Mazzanti, Stefano Cascinu. Impact of single-nucleotide polymorphisms (SNPs) on thymic hyperplasia and tumors outcome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2220. doi:10.1158/1538-7445.AM2014-2220