Transforming growth factor alpha (TGF-alpha) expression in dysplastic oralleukoplakia: Modulation by 13-cis retinoic acid

Background. Surrogate endpoint biomarkers (SEBs) are detectable molecular, cellular, and tissue changes that take place during tumorigenesis and can b e modulated by a chemoprevention agent. Method. To identify candidate SEBs for invasive squamous cell carcinoma of the upper aerodigestive tract (SCC), we have studied the expression of tran sforming growth factor-alpha (TGF-alpha) and epidermal growth factor recept or (EGFr) in sequential biopsy specimens of dysplastic oral leukoplakia and adjacent normal-appearing mucosa. Biopsies were taken from patients before , during, and after treatment with 13-cis retinoic acid, a vitamin A deriva tive. Immunohistochemistry was performed using the Biogenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system. Results. The pretreatment expression of TGF-alpha and EGFr in dysplastic or al leukoplakia was increased when compared with their expression in adjacen t normal-appearing mucosa (p = 0.001 and p = 0.01, respectively). Eleven of 14 patients enrolled in the study (78.6%) completed 3 months of treatment with 13-cis retinoic acid (1.0 mg/kg/day). TGF-alpha expression in dysplast ic oral leukoplakia, but not in adjacent normal-appearing mucosa, decreased during treatment (p < 0.05). Conclusions. TGF-alpha is a candidate SEB for future SCC chemoprevention tr ials. (C) 1999 John Wiley & Sons, Inc.