title: Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy.
abstract: 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.
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.affiliation: Department of Thoracic Surgery, St. James's University Hospital, Leeds, West Yorkshire, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brunelli
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pagliaretta
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Paolucci
authors.affiliation: Urology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Conti
authors.affiliation: Section of Pathological Anatomy and Histopathology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Goteri
authors.affiliation: Thoracic Surgery, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Majed
authors.initials: M
authors.lastname: Refai
authors.affiliation: Department of Thoracic Surgery, St. James's University Hospital, Leeds, West Yorkshire, United Kingdom.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Pompili
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Marcantognini
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Morgese
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Zelmira
authors.initials: Z
authors.lastname: Ballatore
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Savini
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: De Lisa
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Caramanti
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Section of Pathological Anatomy and Histopathology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zizzi
authors.affiliation: Department of Specialistic Clinical and Odontostomatological Sciences, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piva
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mazzanti
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Azzurra
authors.initials: A
authors.lastname: Onofri
authors.affiliation: Thoracic Surgery, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Sabbatini
authors.affiliation: Section of Pathological Anatomy and Histopathology, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Scarpelli
authors.affiliation: Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D013934:Thymectomy / Q000379:methods*; D013945:Thymoma / Q000235:genetics* / Q000601:surgery; D013953:Thymus Neoplasms / Q000235:genetics* / Q000601:surgery; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: angiogenesis; prognosis; single nucleotide polymorphism; thymic epithelial tumor; tumor risk