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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.
AuthorsI Gina Rojas, Alejandra Martínez, Ursula Brethauer, Patricia Grez, Roger Yefi, Sandra Luza, Francisco J Marchesani
JournalOral oncology (Oral Oncol) Vol. 45 Issue 3 Pg. 284-90 (Mar 2009) ISSN: 1879-0593 [Electronic] England
PMID18674950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Receptor, PAR-2
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Tryptases
Topics
  • Adult
  • Aged
  • Case-Control Studies
  • Cell Transformation, Neoplastic
  • Cheilitis (metabolism, pathology)
  • Cyclooxygenase 2 (metabolism)
  • Epithelial Cells (pathology)
  • Female
  • Humans
  • Keratosis, Actinic (metabolism, pathology)
  • Lip Neoplasms (metabolism, pathology)
  • Male
  • Middle Aged
  • Receptor, PAR-2 (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tryptases (metabolism)
  • Young Adult

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