Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: potential markers for aggressive phenotypes.

Polymorphisms of the VEGF gene are known to affect the biological behaviour of cancers but have seldom been studied in thyroid cancer. The aim of the current study is to evaluate the prevalence and relevance of VEGF-A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC). Genomic DNA and total RNA were isolated from paraffin-embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and 78 control thyroid tissues. Three DNA polymorphisms (+936Cxa0>xa0T, +405Cxa0>xa0G and -141Axa0>xa0C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues was studied by real-time PCR. Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141Axa0>xa0C and +405Cxa0>xa0G) and 3'-UTR (VEGF +936Cxa0>xa0T) were all significantly different in PTC and benign thyroid tissue (pxa0=xa00.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (pxa0=xa00.026). VEGF + 405xa0Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (pxa0=xa00.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (pxa0=xa00.009). Within the group of patients with conventional PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA expression than other patients (pxa0=xa00.0003). These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.