title: Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR-2.
abstract: 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.
authors.affiliation: Department of Oral Surgery and Laboratory of Oral Biology and Pathology, College of Dentistry, University of Concepción, Chile. grojas@udec.cl
authors.forename: I Gina
authors.initials: IG
authors.lastname: Rojas
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martínez
authors.forename: Ursula
authors.initials: U
authors.lastname: Brethauer
authors.forename: Patricia
authors.initials: P
authors.lastname: Grez
authors.forename: Roger
authors.initials: R
authors.lastname: Yefi
authors.forename: Sandra
authors.initials: S
authors.lastname: Luza
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Marchesani
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D002613:Cheilitis / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D055623:Keratosis, Actinic / Q000378:metabolism* / Q000473:pathology; D008048:Lip Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044464:Receptor, PAR-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053802:Tryptases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D044464:Receptor, PAR-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D053802:Tryptases