ECE2016 Guided Posters Thyroid Cancer (1) (10 abstracts)
Analysis of germline VEGF-A SNPs allows the identification of a subgroup of ATA low-intermediate risk DTC (differentiated thyroid cancer) patients with poor probability to develop recurrences
Vincenzo Marotta 1 , Concetta Sciammarella 1 , Mario Capasso 1, , Alessandro Testori 1, , Claudio Gambardella 3 , Marica Grasso 4 , Manila Rubino 1 , Maurizio De Palma 4 , Maria Grazia Chiofalo 5 , Claudia Pivonello 1 , Rosario Pivonello 1 , Luigi Santini 3 , Luciano Pezzullo 5 , Annamaria Colao 1 & Antongiulio Faggiano 1,
1Federico II University, Naples, Italy; 2CEINGE “Biotecnologie avanzate”, Naples, Italy; 3Second University of Naples, Naples, Italy; 4Cardarelli Hospital, Naples, Italy; 5INT Pascale, Naples, Italy.
Introduction: Constitution of new blood vessels is crucial for cancer self-maintenance and progression. Neo-angiogenesis may be affected from hereditary traits, namely the presence of SNPs (single nucleotide polymorphisms) of genes involved in its regulation. VEGF-A represents the main regulator of angiogenesis. Germline SNPs of the VEGF-A gene have been associated to outcome of several cancers, but no data exist about differentiated thyroid cancer (DTC).
Patients and methods: Multicenter retrospective study. Blood samples were obtained from consecutive DTC-patients afferent to included centers (Federico II University, “INT Pascale” Institute, “Cardarelli” Hospital, Second University of Naples). Four VEGF-A SNPs (rs2010963, rs699947, rs833061, rs3025039) were chosen basing on their probable functional impact and genotyped using TaqMan protocol (Applied biosystems StepOnePlus). Clinico-pathological data at diagnosis and prognostic outcome were retrieved. The genotypes were analyzed as a three-group categorical variable (reference model) and according to the dominant and recessive model. Linkage disequilibrium (LD) was analyzed using HAPLOVIEW. Primary endpoint was rate of recurrent disease.
Results: Overall, 249 patients were included. Allele frequencies were consistent with data from the National Center for Biotechnology Information Databank. Genotype frequencies were in Hardy–Weinberg equilibrium (P>0.05). Outcome analysis was restricted to 226 patients classified as low-intermediate risk of recurrence according to ATA (America Thyroid Association) system, having a median follow-up of 4 years. Homozygous minor allele genotypes of rs699947 and rs833061 SNPs (A/A and C/C, respectively) were associated with a significantly lower rate of recurrent disease (P=0.035 and 0.031, respectively). rs699947 and rs833061 SNPs were in LD (D’=1). The combination of the genotypes A/A of rs699947 and C/C of rs833061 had PPV of non-recurrent disease of 97.3% (95%CI 85.84–99.93).
Conclusions: Analysis of germline VEGF-A SNPs refines risk stratification of DTC by identifying a subgroup of ATA low-intermediate patients with excellent prognosis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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