Cyclooxygenase-2 (COX-2) is overexpressed in various types of human
malignancies, including
oral cancers. Recent studies have shown that mast cell-derived
protease tryptase can induce COX-2 expression by the cleavage of
proteinase-activated receptor-2 (PAR-2).
Actinic cheilitis (AC) is a premalignant form of
lip cancer characterized by an increased density of
tryptase-positive mast cells. To investigate the possible contribution of
tryptase to COX-2 overexpression during early lip
carcinogenesis, normal lip (n=24) and AC (n=45) biopsies were processed for COX-2, PAR-2 and
tryptase detection, using RT-PCR and immunohistochemistry. Expression scores were obtained for each marker and tested for statistical significance using Mann-Whitney and Spearmann's correlation tests as well as multivariate logistic regression analysis. Increased epithelial co-expression of COX-2 and PAR-2, as well as, elevated subepithelial density of
tryptase-positive mast cells were found in AC as compared to normal lip (P<0.001). COX-2 overexpression was found to be a significant predictor of AC (P<0.034, forward stepwise, Wald), and to be correlated with both
tryptase-positive mast cells and PAR-2 expression (P<0.01). The results suggest that epithelial COX-2 overexpression is a key event in AC, which is associated with increased
tryptase-positive mast cells and PAR-2. Therefore,
tryptase may contribute to COX-2 up-regulation by epithelial PAR-2 activation during early lip
carcinogenesis.