title: Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases.
abstract: BACKGROUND
  Cyclooxygenase (COX)-2 expression and tumour-induced angiogenesis appear to be increased in squamous cell carcinoma (SCC) of the skin. In other cancers, COX-2 is a pro-angiogenic factor. The association between angiogenesis and COX-2 has not been studied in skin cancer.
  
  
  OBJECTIVE
  To assess the onset of increased COX-2 expression and angiogenesis in the multistage carcinogenesis of SCC as well as the correlation between those two parameters.
  
  
  METHODS
  We performed a retrospective paired immunohistochemical analysis of normal skin, actinic keratosis (AK), Bowen's disease (BD) and SCC among 35 individuals. Specimens were considered COX-2 immunopositive when 5% or more of the tumour cells showed clear evidence of immunostaining. To quantify active angiogenesis, we used a Ki-67-CD34 double-labelling immunohistochemical stain and calculated the fraction of proliferating endothelial cells. The Chalkley method was used to determine the microvessel density. To detect hypoxia, a carboanhydrase IX immunostain was used.
  
  
  RESULTS
  Compared with normal epidermis (0%), AK (31%), BD (22%) and SCC (40%) were significantly more likely to be COX-2 immunopositive (P < 0.01). The fraction of proliferating endothelial cells and the Chalkley scores paralleled multistage carcinogenesis (P < 0.05 between different stages). COX-2 immunopositivity was fairly correlated with hypoxia and higher proliferating endothelial cell fractions but not with Chalkley counts.
  
  
  CONCLUSIONS
  Induction of COX-2 expression and angiogenesis are both early events in the development of SCC. In addition to ultraviolet light, hypoxia and COX-2 may be involved in skin tumour angiogenesis.
authors.affiliation: Pathology, University of Antwerp, Antwerp, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Nijsten
authors.forename: C G
authors.initials: CG
authors.lastname: Colpaert
authors.forename: P B
authors.initials: PB
authors.lastname: Vermeulen
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: E
authors.initials: E
authors.lastname: Van Marck
authors.forename: J
authors.initials: J
authors.lastname: Lambert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001913:Bowen's Disease / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D015687:Cell Hypoxia; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D007642:Keratosis / Q000201:enzymology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D011230:Precancerous Conditions / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases