title: Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study.
abstract: BACKGROUND
  New blood vessel formation events are essential for tumor clonal expansion and progression. Despite the importance of vascular endothelial growth factor A (VEGFA) for tumor angiogenesis, few studies have evaluated the expression profile of this gene in oral squamous cell carcinoma (OSCC) and tumor margins (TM). This study aimed to evaluate the expression of the VEGFA gene and its protein in OSCC and TM.
  
  
  METHODS
  Gene expression was evaluated in cryopreserved samples of OSCCs (n = 44), TM (n = 7), and normal mucosa from healthy patients (n = 3; NM). Quantitative PCRs were performed using the TaqMan system for the VEGFA gene, and gene expression was determined using the 2(-∆∆CQ) method. For immunohistochemical evaluation, 27 OSCC samples were embedded in a tissue microarray (TMA) block and reactions were performed using the Advance system.
  
  
  RESULTS
  VEGFA transcript levels were 1.7-fold higher in OSCC than in NM samples. VEGFA mRNA was overexpressed in TM samples compared to NM (3.4-fold) and OSCC (2.0-fold) samples. VEGFA transcript level was overexpressed in T3-T4 tumors, metastatic lymph nodes, and stage III-IV OSCCs. Immunoreactivity of the VEGFA protein was detected in the cytoplasm of parenchymal and stromal cells, mainly in endothelial cells and fibroblasts.
  
  
  CONCLUSIONS
  Our results show that VEGFA was overexpressed in aggressive OSCCs and that VEGFA expression may be an important prognostic factor in this type of cancer. Finally, tumor margins may be involved in the production of angiogenic molecules.
authors: Federal University of Bahia, Salvador, Brazil.
authors: Caroline Brandi Schlaepfer
authors: CB
authors: Sales
authors: AC Camargo Cancer Center, São Paulo, Brazil.
authors: Marcilei Eliza Cavichiolli
authors: ME
authors: Buim
authors: Federal University of Bahia, Salvador, Brazil.
authors: Renata Oliveira
authors: RO
authors: de Souza
authors: Oswaldo Cruz Foudation, Gonçalo Moniz Research Center, Laboratory of Pathology and Molecular Biology, Salvador, Brazil.
authors: Ludmila
authors: L
authors: de Faro Valverde
authors: Oswaldo Cruz Foudation, Gonçalo Moniz Research Center, Laboratory of Pathology and Molecular Biology, Salvador, Brazil.
authors: Maria Cecília
authors: MC
authors: Mathias Machado
authors: Federal University of Bahia, Salvador, Brazil.|Oswaldo Cruz Foudation, Gonçalo Moniz Research Center, Laboratory of Pathology and Molecular Biology, Salvador, Brazil.
authors: Mitermayer Galvão
authors: MG
authors: Reis
authors: AC Camargo Cancer Center, São Paulo, Brazil.
authors: Fernando Augusto
authors: FA
authors: Soares
authors: Federal University of Bahia, Salvador, Brazil.|Oswaldo Cruz Foudation, Gonçalo Moniz Research Center, Laboratory of Pathology and Molecular Biology, Salvador, Brazil.
authors: Eduardo Antônio Gonçalves
authors: EA
authors: Ramos
authors: Federal University of Bahia, Salvador, Brazil.|Oswaldo Cruz Foudation, Gonçalo Moniz Research Center, Laboratory of Pathology and Molecular Biology, Salvador, Brazil.
authors: Clarissa Araújo
authors: http://orcid.org/0000-0001-8922-2985
authors: CA
authors: Gurgel Rocha
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis; 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
keywords: immunohistochemistry; oral cancer; real-time polymerase chain reaction; vascular endothelial growth factor