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Int J Clin Exp Pathol 2012;5(1):58-71

Original Article
Idiopathic pulmonary fibrosis: immunohistochemical analysis provides fresh insights
into lung tissue remodelling with implications for novel prognostic markers

Nicola J Lomas, Keira L Watts, Khondoker M Akram, Nicholas R Forsyth, Monica A Spiteri

Department of Cellular Pathology, University Hospital of North Staffordshire, UK; Lung Research Group, Institute of Science and Technology in
Medicine, Keele University, UK; Department of Respiratory Medicine, University Hospital of North Staffordshire, UK.

Received November 25, 2011; accepted January 3, 2011; Epub January 7, 2012; published January 15, 2012

Abstract: Aim: This study explored the cellular and biological interrelationships involved in Idiopathic Pulmonary Fibrosis (IPF) lung tissue
remodelling using immunohistochemical analysis. Methods and results: IPF and control lung tissues were examined for localisation of
Epithelial Mesenchymal Transition (EMT), proliferation and growth factor markers assessing their relationship to key histological aberrations. E-
cadherin was expressed in IPF and control (Alveolar type II) ATII cells (>75%). In IPF, mean expression of N-cadherin was scanty (<10%):
however 4 cases demonstrated augmented expression in ATII cells correlating to histological disease status (Pearson correlation score
0.557). Twist was expressed within fibroblastic foci but not in ATII cells. Transforming Growth Factor- β (TGF-β) protein expression was
significantly increased in IPF ATII cells with variable expression within fibroblastic foci.  Antigen Ki-67 was observed within hyperplastic ATII
cells but not in cells overlying foci. Collagen I and α-smooth muscle actin (α-SMA) were strongly expressed within fibroblastic foci (>75%);
cytoplasmic collagen I in ATII cells was present in 3 IPF cases. IPF ATII cells demonstrated variable Surfactant Protein-C (SP-C). Conclusions:
The pathogenesis of IPF is complex and involves multiple factors, possibly including EMT. Histological analysis suggests TGF-β-stimulated
myofibroblasts initiate a contractile response within established fibroblastic foci while proliferating ATII cells attempt to instigate alveolar
epithelium repair. Marker expression (N-cadherin and Ki-67) correlation with histological disease activity (as reflected by fibroblastic foci extent)
may emerge as future prognostic indicators for IPF.  (IJCEP1111014).

Keywords: Idiopathic Pulmonary Fibrosis, immunohistochemistry, epithelial-mesenchymal transition, tissue repair and remodelling,
prognostic markers

Address all correspondence to:
Dr Keira L Watts, PhD
Institute of Science and Technology in Medicine
Guy Hilton Research Centre
Keele University
Staffordshire, UK.
Tel: 01782 554224
E-mail: keira.watts@uhns.nhs.uk