Prognostic value of vascular endothelial growth factors A and C in oral squamous cell carcinoma

J Oral Pathol Med. 2014 Aug;43(7):514-20. doi: 10.1111/jop.12167. Epub 2014 Apr 25.

Abstract

Background: Vascular endothelial growth factor (VEGF) family members play a major role in angiogenesis and vascularization. VEGF-A promotes tumor angiogenesis by stimulating the growth of tumor vascular endothelial cells. In addition, VEGF-C has been identified as a potent inducer of lymphangiogenesis in tumor and lymph node metastasis. Previous studies have investigated the association between clinicopathological factors and the expression of VEGF-A and VEGF-C in oral squamous cell carcinoma cancer (OSCC), but the results are contradictory. In this study, we investigated the relationship between VEGF-A and VEGF-C expression and OSCC clinicopathological factors and prognosis.

Methods: Expression of VEGF-A and VEGF-C was evaluated in surgical specimens from 61 patients with OSCC and three human oral cancer cell lines (OSC-19, OSC-20 and HOC313) by immunohistochemical staining and enzyme-linked immunosorbent assay, respectively. We also determined the relationship between the 5-year survival rate and clinicopathological factors, such as TNM classification (Union for International Cancer Control, UICC), lymph node metastasis, recurrence, histological differentiation, location, and mode of invasion.

Results: VEGF-A expression correlated significantly with lymph node metastasis. VEGF-C expression was associated with lymph node metastasis, recurrence, and a poorer 5-year survival rate. A multivariate analysis demonstrated that VEGF-C is an independent prognostic factor for patients with OSCC. VEGF-C expression was significantly up-regulated in HOC313 cells compared to OSC-19 and OSC-20 cells.

Conclusions: These results indicate that VEGF-C may be a predictive factor for OSCC outcome, lymph node metastasis, and recurrence. Moreover, VEGF-C may be an important factor in the development of new therapies for OSCC patients.

Keywords: VEGF-A; VEGF-C; immunohistochemistry; oral squamous cell carcinoma; prognosis.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / secondary
  • Cell Line, Tumor
  • Female
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / chemistry*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate
  • Vascular Endothelial Growth Factor A / analysis*
  • Vascular Endothelial Growth Factor C / analysis*

Substances

  • Biomarkers, Tumor
  • VEGFA protein, human
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C