Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases.
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.
Nijsten
T
T
Pathology, University of Antwerp, Antwerp, Belgium.
Colpaert
C G
CG
Vermeulen
P B
PB
Harris
A L
AL
Van Marck
E
E
Lambert
J
J
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
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases