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

Academic Article


  • 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.
  • Published In


  • Antineoplastic Agents, Biomarkers, Tumor, Biopsy, Carcinoma, Squamous Cell, Chemoprevention, ErbB Receptors, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Immunohistochemistry, Isotretinoin, Keratolytic Agents, Leukoplakia, Oral, Mouth Mucosa, Pilot Projects, Single-Blind Method, Transforming Growth Factor alpha
  • Author List

  • Beenken SW; Sellers MT; Huang P; Peters G; Krontiras H; Dixon P; Stockard C; Listinsky C; Grizzle WE
  • Start Page

  • 566
  • End Page

  • 573
  • Volume

  • 21
  • Issue

  • 6