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Comparative Study
. 1999 Sep;21(6):566-73.
doi: 10.1002/(sici)1097-0347(199909)21:6<566::aid-hed11>3.0.co;2-h.

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

S W Beenken  1 , M T Sellers, P Huang, G Peters, H Krontiras, P Dixon, C Stockard, C Listinsky, W E Grizzle
Affiliations
Comparative Study

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

S W Beenken et al. Head Neck. 1999 Sep.

Abstract

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-alpha (TGF-alpha) and epidermal growth factor receptor (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 derivative. 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 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-alpha expression in dysplastic 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 trials.

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