Quantitative immunohistochemical analysis of transforming growth factor-alpha and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck

Cancer. 1996 Sep 15;78(6):1284-92. doi: 10.1002/(SICI)1097-0142(19960915)78:6<1284::AID-CNCR17>3.0.CO;2-X.


Background: Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) mRNA are up-regulated in squamous cell carcinoma of the head and neck (SCCHN) tissues.

Methods: Immunohistochemical staining with monoclonal antibodies to TGF-alpha and EGFR was undertaken to identify the cellular origin in tissue obtained from cancer patients and controls and to determine the correlation between mRNA expression levels and two methods of immunohistochemical evaluation.

Results: TGF-alpha protein staining occurred in the suprabasal layers and spared the basal layer of normal controls. Conversely, in histologically normal mucosa from SCCHN patients, TGF-alpha was present throughout the epithelium, including the basal layer. EGFR staining was negligible in normal mucosa from control patients without cancer and relatively increased in SCCHN tissues. Increasing staining intensity was correlated with worsening dysplasia and closer proximity to the tumor. Using computerized image analysis to quantify the intensity of immunostaining, the mean optical density (MOD) of TGF-alpha staining in histologically normal mucosa (P = 0.049) and tumors (P = 0.005) from SCCHN patients was significantly higher than in control normal mucosa from noncancer patients (1.9- and 1.7-fold, respectively). EGFR MOD was also greater in the histologically normal mucosa (P = 0.009) and tumors (P = 0.006) from SCCHN patients than in control normal mucosa (1.8- and 1.9-fold, respectively). For both TGF-alpha (P = 0.668) and EGFR (P = 0.116), the MOD was similar for both tumor and histologically normal mucosa from SCCHN patients.

Conclusions: TGF-alpha and EGFR protein expression is increased early in head and neck squamous cell carcinogenesis and can be quantitated by computerized image analysis of immunohistochemical staining. Altered distribution of TGF-alpha protein in histologically normal mucosa from SCCHN patients compared with control mucosa from patients without cancer suggests a switch from a paracrine to an autocrine pathway.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / pathology*
  • Cell Nucleus / ultrastructure
  • Coloring Agents
  • Cytoplasm / ultrastructure
  • Epithelium / pathology
  • ErbB Receptors / analysis*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Hypopharyngeal Neoplasms / pathology
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Laryngeal Neoplasms / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / pathology
  • Mucous Membrane / pathology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Tumor Necrosis Factor-alpha / analysis*
  • Up-Regulation


  • Coloring Agents
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • ErbB Receptors