title: Evaluation of hypoxia, angiogenesis, and lymphangiogenesis in actinic cheilitis.
abstract: BACKGROUND
  Actinic cheilitis is a potentially malignant condition caused mainly by chronic sun exposure. Here we aim to evaluate the role of hypoxia, angiogenesis, and lymphatic density in the clinical and morphological progression of a series of cases of actinic cheilitis.
  
  
  METHODS
  Immunohistochemistry was used to evaluate positivity to hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF)-C, and D2-40 in 40 cases of actinic cheilitis of the lower lip.
  
  
  RESULTS
  The cases studied exhibited variable degrees of positivity to the markers. The median number of lymphatic vessels was 3.2, 2.4, and 3.0 in lesions showing no epithelial dysplasia (NED) and with mild (MED) and moderate (MOED) epithelial dysplasia, respectively. The median VEGF-C positivity index was 82.44% (NED), 92.74% (MED), and 82.83% (MOED), and the median HIF-1α positivity index was 11.57% (NED), 5.26% (MED), and 13.55% (MOED). No significant differences in lymphatic density or median VEGF-C and HIF-1α positivity indices were observed between histological grades or clinical presentations of actinic cheilitis (P > 0.05).
  
  
  CONCLUSIONS
  Although representing early events in lip carcinogenesis, the present results suggest that hypoxia, angiogenesis, and lymphangiogenesis do not influence the morphological or clinical progression of actinic cheilitis.
authors.affiliation: Oral Pathology Post-Graduate Program, Federal University of Rio Grande do Norte, Natal, Brazil. nataliagbarbosa@gmail.com.
authors.forename: Natália G
authors.initials: NG
authors.lastname: Barbosa
authors.affiliation: Oral Pathology Post-Graduate Program, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Lélia B
authors.initials: LB
authors.lastname: Souza
authors.affiliation: Department of Dentistry, State University of Paraiba, Campina Grande, Brazil.
authors.forename: Cassiano F W
authors.initials: CF
authors.lastname: Nonaka
authors.affiliation: Oral Pathology Post-Graduate Program, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Ericka J D
authors.initials: EJ
authors.lastname: Silveira
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015687:Cell Hypoxia; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000473:pathology; D002613:Cheilitis / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D008046:Lip / Q000098:blood supply; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis*; D055815:Young Adult; D000098853:Podoplanin
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008562:Membrane Glycoproteins; D042582:Vascular Endothelial Growth Factor C; C497442:HIF1A protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C467486:VEGFC protein, human