Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung.

Academic Article

Abstract

  • PURPOSE: This study was conducted to evaluate the clinical significance of the localization of epidermal growth factor receptor (EGF-r), transforming growth factor (TGF)-alpha, and erbB-2 in the development, progression and prognosis of squamous cell cancers (SCCs) of the lung. EXPERIMENTAL DESIGN: The localization of EGF-r, TGF-alpha, and erbB-2 was evaluated immunohistochemically in 60 archival specimens of SCC of the lung and in 60 lung specimens without cancer. To clarify the patterns of expression of EGF-r in these tumors, the patterns of expression of EGF-r in cells in culture were monitored after challenging normal human bronchial epithelial and SCC cell lines with either EGF or TGF-alpha at physiological concentrations. RESULTS AND CONCLUSIONS: The expression of EGF-r, erbB-2, and TGF-alpha were significantly higher in SCC and associated precancerous lesions than in the normal bronchial epithelium and hyperplastic lesions of noncancer specimens. A statistically significant stepwise increase in expression from uninvolved bronchial epithelium to precancerous lesions to SCC was observed with EGF-r and TGF-alpha. The localization of EGF-r in the cytoplasm (P = 0.04), but not in the membrane (P = 0.20), of SCCs was significantly associated with poor overall survival of subjects. To demonstrate the biological relevance of cytoplasmic expression of EGF-r, we noted that there was a prompt reduction in the membrane expression and a concomitant increase in cytoplasmic expression of EGF-r after adding either EGF or TGF-alpha to the cell culture medium. Overall, the study identified an involvement of EGF-r and TGF-alpha in the development of SCCs. The prognostic importance of EGF-r expression in the cytoplasm of lung cancer probably is an indication of the prognostic importance of trafficking of the EGF-r receptor between the Golgi apparatus and cell membranes and of internalization of EGF-r after an interaction with one of the EGF-r ligands at the cellular membrane surface.
  • Published In

    Keywords

  • Carcinoma, Squamous Cell, Cell Membrane, Cytoplasm, Epithelial Cells, ErbB Receptors, Humans, Hyperplasia, Immunoenzyme Techniques, Ligands, Lung Neoplasms, Precancerous Conditions, Prognosis, Receptor, ErbB-2, Survival Rate, Transforming Growth Factor alpha, Tumor Cells, Cultured
  • Pubmed Id

  • 15301417
  • Author List

  • Piyathilake CJ; Frost AR; Manne U; Weiss H; Bell WC; Heimburger DC; Grizzle WE
  • Start Page

  • 734
  • End Page

  • 744
  • Volume

  • 8
  • Issue

  • 3