title: Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Department Nutrition Sciences, Heidi Weiss Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. piyathic@uab.edu
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
authors.forename: Andra R
authors.initials: AR
authors.lastname: Frost
authors.forename: Uppender
authors.initials: U
authors.lastname: Manne
authors.forename: Heidi
authors.initials: H
authors.lastname: Weiss
authors.forename: Walter C
authors.initials: WC
authors.lastname: Bell
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Heimburger
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane; D003593:Cytoplasm / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000473:pathology
chemical_list: D066246:ErbB Receptors; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha