Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis

Background and Aim: A recent transgenic mouse model overexpressing transfor ming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibros is. In order to validate this mouse as a model for idiopathic pulmonary fib rosis in humans, we studied the expression of TGF-alpha in lung tissue of p atients with idiopathic pulmonary fibrosis compared to control lung tissue. Methods: Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron s ections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immun ohistochemistry system. Four cell types were examined (vascular endothelium , bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain acti vity was scored on a six point scale. Results: Eleven patients with IPF wer e compared to seven control subjects. TGF-alpha immunoreactivity was signif icantly higher in the IPF patients than in controls in the vascular endothe lium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF- R, one of the receptors for TGF-alpha, between these two patient population s were not as striking. There was a small but significantly greater express ion of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. Conclusions: TGF-alpha is overexpressed in patients with IPF, esp ecially in the vascular endothelial cells.