Microvessel density and VEGF, HIF-1α expression in primary oral melanoma: correlation with prognosis

Oral Dis. 2013 Sep;19(6):620-7. doi: 10.1111/odi.12048. Epub 2012 Dec 27.

Abstract

Objective: To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM).

Materials and methods: Sixteen malignant primary melanomas were immunostained with markers CD34, VEGF and HIF-1α. Stained cells were counted in the invasive front and inside the tumour, and the differences were compared and correlated with histological parameters and disease-specific survival of the patients.

Results: Tumour invasive front showed increased MVD and increased vessel VEGF and HIF-1α expression compared with the intratumoural compartment. No such differences were seen in tumoural melanocytes of the two compartments. Positive correlations were observed between CD34 and VEGF, CD34 and HIF-1α and VEGF and HIF-1α expression in invasive front vessels. CD34 expression was statistically correlated with the level of infiltration. A significant trend to worse disease-free survival was also determined with increased invasive front vessel expression of CD34, VEGF and HIF-1α.

Conclusions: Our data highlight the importance of the invasive margin in POM biology. The high angiogenic activity and endothelial VEGF and HIF-1α expression in invasive front vessels have a significant impact on patient survival and future agents targeted against VEGF pathway may represent a novel and effective therapeutic opportunity. Larger studies are needed to further address our findings.

Keywords: HIF-1α; MVD; VEGF; invasive margin; oral melanoma; survival.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / analysis
  • Disease Progression
  • Disease-Free Survival
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Hypoxia / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis*
  • Immunohistochemistry
  • Male
  • Melanocytes / pathology
  • Melanoma / blood supply*
  • Melanoma / pathology
  • Microvessels / pathology*
  • Middle Aged
  • Mouth Neoplasms / blood supply*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / pathology
  • Palatal Neoplasms / blood supply
  • Palatal Neoplasms / pathology
  • Prognosis
  • Sex Factors
  • Survival Rate
  • Vascular Endothelial Growth Factor A / analysis*

Substances

  • Antigens, CD34
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A