title: Microvessel density and VEGF, HIF-1α expression in primary oral melanoma: correlation with prognosis.
abstract: OBJECTIVE
  To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM).
  
  
  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.
authors.affiliation: Department of Clinic and Molecular Sciences-Dermatology, Marche Polytechnic University, Ancona, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Simonetti
authors.forename: G
authors.initials: G
authors.lastname: Lucarini
authors.forename: C
authors.initials: C
authors.lastname: Rubini
authors.forename: G
authors.initials: G
authors.lastname: Goteri
authors.forename: A
authors.initials: A
authors.lastname: Zizzi
authors.forename: S
authors.initials: S
authors.lastname: Staibano
authors.forename: A
authors.initials: A
authors.lastname: Campanati
authors.forename: G
authors.initials: G
authors.lastname: Ganzetti
authors.forename: R
authors.initials: R
authors.lastname: Di Primio
authors.forename: A
authors.initials: A
authors.lastname: Offidani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology; D010157:Palatal Neoplasms / Q000098:blood supply / Q000473:pathology; D011379:Prognosis; D012737:Sex Factors; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: D018952:Antigens, CD34; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: HIF-1α; MVD; VEGF; invasive margin; oral melanoma; survival