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Apoptosis & Physiological Markers:oral Preneoplasia/Squamous

#C121 Apoptosis and Physiological Markers of Oral Pre-neoplasia and Squamous Cell Carcinoma.

Robert J. Griffin,1 Brent W. Williams,1 Bin Cheng,2 Nelson L. Rhodus.3 Univ. of Minnesota Medical School,1

Minneapolis, MN, Sun Yat-Sen University,2 Guangzhou, China, University of Minnesota Dental School,3 Minneapolis, MN.

Previous humanand animal model studies indicate that there is an abnormal degree of apoptosis and apoptotic gene expression during oral carcinogenesis, although the results are conflicting and evaluation of their clinical significance has not been validated.

We have begun to identify and measure apoptotic activity in whole saliva and biopsies from patients with oral pre-malignant and malignant lesions to explore the feasibility of using apoptotic index for prognostic purposes.

Volunteers with no lesions, oral leukoplakia and/or lichen planus and patients with oral squamous cell carcinoma donated saliva. Cells were collected and analyzed for apoptosis using a modified fluorescent TUNEL technique (APO-Brdu-TUNEL).

The fraction of apoptotic cells in patients previously treated fororal cancerwas significantly higher (18.18 12%) than in healthy volunteers(6.99 6.1%) orindividuals with pre-neoplastic conditions(4.4 2.75%).

Patients with previously untreated malignant lesions had the lowest apoptotic index in saliva at 3.4 2.5%.

These results suggest that apoptosis may be a marker for treatment efficacy in cancer patients and may give insight into which patients with pre-malignant lesions are at risk for developing cancer.

We are currently analyzing brush and punch biopsies in addition to saliva samples with multiple apoptosis assays to determine the mostaccurate and meaningful route of measurement.

We are concurrently measuring the expression of HIF1-á (a marker of hypoxia) and NQO1 (a detoxifying enzyme known to be upregulated in malignant cells) in our three classes of patients (healthy, pre-malignant and malignant) to provide further insight anddevelop accessible prognostic tools for oral carcinogenesis.

Frontiers in Cancer Prevention Research, 2003 AACR

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