Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung.
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.
Piyathilake
Chandrika J
CJ
Department Nutrition Sciences, Heidi Weiss Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. piyathic@uab.edu
Frost
Andra R
AR
Manne
Uppender
U
Weiss
Heidi
H
Bell
Walter C
WC
Heimburger
Douglas C
DC
Grizzle
William E
WE
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
D066246:ErbB Receptors; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha