Biomarker expression during oral carcinogenesis using an in vivo imaging approach.

A33

Background and Objective: Oral carcinogenesis is a multistep process in which genetic events cause disruption of the normal regulatory pathways controlling basic cellular function, Multiple genetic events lead to oral cancer, and various cellular genes are overexpressed in oral squamous cell carcinoma. Goal of these studies was to image and quantify expression of specific biomarkers known to play a role in the vascular and extracellular matrix (ECM) changes. Study Design/Materials and Methods: In the hamster cheek model (30 hamsters) throughout carcinogenesis, in vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques were used to image surface and subsurface fluorescence prior to and after the injection of biomarkers: Vascular Endothelial Growth Factor (VEGF); urinase type Plasminogen Activator (uPA) and Inhibitor (PAI-1); Matrix Metalloproteinases 1,2,9 (MMPs). At 0,4,6,8,10,12 weeks, one animal was sacrificed., Histopathological sections were prepared and pathology evaluated on a scale of 0-6. Results: Carcinogenesis-related structural and vascular changes were clearly visible. Biomarker expression was clearly identified, localized and quantified at all timepoints throughout carcinogenesis, providing important new information on the carcinogenesis process. Conclusion: Time- and spatially-resolved determination of (1) specific biomarker expression, (2) vascular and ECM changes throughout oral carcinogenesis provide valuable information on mechanisms of dysplastic and malignant change. Supported by: CRFA 30003, NIH (LAMMP) P41 RR01192, AFOSR FA 9550-04-1-0101, CA TRDRP 445174-18079.