title: Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: potential markers for aggressive phenotypes.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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 (+936C > T, +405C > G and -141A > C) 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.
  
  
  RESULTS
  Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (p = 0.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (p = 0.009). 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 (p = 0.0003).
  
  
  CONCLUSIONS
  These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.
authors.affiliation: Cancer Molecular Pathology, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Salajegheh
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Kasem
authors.forename: V
authors.initials: V
authors.lastname: Gopalan
authors.forename: M R
authors.initials: MR
authors.lastname: Nassiri
authors.forename: R
authors.initials: R
authors.lastname: William
authors.forename: A K Y
authors.initials: AK
authors.lastname: Lam
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A