Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study

J Oral Pathol Med. 2016 Aug;45(7):481-5. doi: 10.1111/jop.12398. Epub 2016 Feb 10.

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.

Conclusion: 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.

Keywords: immunohistochemistry; oral cancer; real-time polymerase chain reaction; vascular endothelial growth factor.

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cytoplasm / metabolism
  • Disease Progression
  • Gene Expression
  • Head and Neck Neoplasms / blood supply
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Mouth Neoplasms / blood supply
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck
  • Tissue Array Analysis
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A