Clinical Research Papers:

Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy

Rossana Berardi _, Alessandro Brunelli, Silvia Pagliaretta, Vittorio Paolucci, Alessandro Conti, Gaia Goteri, Majed Refai, Cecilia Pompili, Giulia Marcantognini, Francesca Morgese, Zelmira Ballatore, Agnese Savini, Mariagrazia De Lisa, Miriam Caramanti, Matteo Santoni, Antonio Zizzi, Francesco Piva, Paola Mazzanti, Azzurra Onofri, Armando Sabbatini, Marina Scarpelli and Stefano Cascinu

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Oncotarget. 2015; 6:19305-19315. https://doi.org/10.18632/oncotarget.4191

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Rossana Berardi1, Alessandro Brunelli2, Silvia Pagliaretta1, Vittorio Paolucci1, Alessandro Conti4, Gaia Goteri5, Majed Refai3, Cecilia Pompili2, Giulia Marcantognini1, Francesca Morgese1, Zelmira Ballatore1, Agnese Savini1, Mariagrazia De Lisa1, Miriam Caramanti1, Matteo Santoni1, Antonio Zizzi5, Francesco Piva6, Paola Mazzanti1, Azzurra Onofri1, Armando Sabbatini3, Marina Scarpelli5, Stefano Cascinu1

1Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I – GM Lancisi – G Salesi, Italy

2Department of Thoracic Surgery, St. James’s University Hospital, Leeds, West Yorkshire, United Kingdom

3Thoracic Surgery, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I – GM Lancisi – G Salesi, Italy

4Urology, Università Politecnica delle Marche, Ancona, Italy

5Section of Pathological Anatomy and Histopathology, Università Politecnica delle Marche, Ancona, Italy

6Department of Specialistic Clinical and Odontostomatological Sciences, Università Politecnica delle Marche, Ancona, Italy

Correspondence to:

Rossana Berardi, e-mail: [email protected]

Keywords: angiogenesis, prognosis, single nucleotide polymorphism, thymic epithelial tumor, tumor risk

Received: April 04, 2015     Accepted: May 26, 2015     Published: June 08, 2015


We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome.

DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays.

As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05).

Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.

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