Deregulated Cyclooxygenase-2 Expression in Oral Premalignant Tissues 1 Supported by Phillip Morris Incorporated (J. K. V.) and National Cancer Institute Grant T30CA36727. 1

Establishment of an early and reliable biomarker for oral carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Cyclooxygenases (COXs) have been implicated previously in several human malignancies, and the therapeutic benefit of specific COX-2 inhibitors has been elucidated. The expression of COX-2 and subsequent markers of malignant progression was studied in archival human specimens representing premalignant and malignant stages of oral cancer. We find that changes in COX-2 gene expression precede changes in expression of biomarkers related to apoptosis and angiogenesis in oral premalignant tissues as a veritable phenotype. We also report for the first time COX-2 mRNA variants in dysplastic samples and in a human papillomavirus-transformed cell line HOK-16B, indicating a possible stabilization of COX-2 message by human papillomavirus infection as an early event in oral cancer. Expression of other markers of tumor progression related to apoptosis and angiogenesis pathway genes shows relatively low level of changes in oral premalignant tissue. However, a determinant shift toward decrease in antitumor immunity was observed by cytokine gene expression profile changes.