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

Background and Aim: A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-α) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-α in lung tissue of patients 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 sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-α or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. Results: Eleven patients with IPF were compared to seven control subjects. TGF-α immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, 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-α, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. Conclusions: TGF-α is overexpressed in patients with IPF, especially in the vascular endothelial cells.