Transforming growth factor α (TGF-α) expression in dysplastic oral leukoplakia: Modulation by 13-cis retinoic acid

✍ Scribed by Samuel W. Beenken; Marty T. Sellers; Peter Huang; Glenn Peters; Helen Krontiras; Pam Dixon; Cecil Stockard; Catherine Listinsky; William E. Grizzle

• Book ID: 101246297
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 152 KB
• Volume: 21
• Category: Article
• ISSN: 1043-3074
• DOI: 10.1002/(sici)1097-0347(199909)21:6<566::aid-hed11>3.0.co;2-h

✦ Synopsis

Background. Surrogate endpoint biomarkers (SEBs) are detectable molecular, cellular, and tissue changes that take place during tumorigenesis and can be 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 transforming growth factor-␣ (TGF-␣) and epidermal growth factor receptor (EGFr) in sequential biopsy specimens of dysplastic oral leukoplakia and adjacent normalappearing mucosa. Biopsies were taken from patients before, during, and after treatment with 13-cis retinoic acid, a vitamin A derivative. Immunohistochemistry was performed using the Biogenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system.

Results. The pretreatment expression of TGF-␣ and EGFr in dysplastic oral leukoplakia was increased when compared with their expression in adjacent 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-␣ expression in dysplastic oral leukoplakia, but not in adjacent normal-appearing mucosa, decreased during treatment (p < 0.05).

Conclusions. TGF-␣ is a candidate SEB for future SCC chemoprevention trials.