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Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions

Authors' Affiliations: ¹ Department of Oral and Maxillofacial Surgery, Anesthesiology and Pathology, College of Dentistry, ² Department of Orthodontics, College of Dentistry, ³ Comprehensive Cancer Center and Solove Research Institute, ⁴ Department of Internal Medicine, College of Medicine, and ⁵ Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio and ⁶ Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Requests for reprints: Susan R. Mallery, Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry, The Ohio State University, Columbus, OH 43210-1241. Phone: 614-292-5892; Fax: 614-292-9384; E-mail: mallery.1{at}osu.edu.

Purpose: The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene–associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties.

Experimental Design: Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes.

Results: Confirming earlier phase I data, none of the 27 participants developed FBR gel–associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene–associated loci.

Conclusions: These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted.