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

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


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biopsy
  • Carcinoma, Squamous Cell / pathology
  • Chemoprevention
  • ErbB Receptors / analysis
  • ErbB Receptors / drug effects
  • ErbB Receptors / genetics
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Isotretinoin / administration & dosage
  • Isotretinoin / adverse effects
  • Isotretinoin / therapeutic use*
  • Keratolytic Agents / administration & dosage
  • Keratolytic Agents / adverse effects
  • Keratolytic Agents / therapeutic use*
  • Leukoplakia, Oral / drug therapy
  • Leukoplakia, Oral / pathology*
  • Mouth Mucosa / drug effects
  • Mouth Mucosa / pathology
  • Pilot Projects
  • Single-Blind Method
  • Transforming Growth Factor alpha / analysis*
  • Transforming Growth Factor alpha / drug effects
  • Transforming Growth Factor alpha / genetics


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Keratolytic Agents
  • Transforming Growth Factor alpha
  • ErbB Receptors
  • Isotretinoin