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Int J Clin Exp Pathol. 2012;5(1):58-71. Epub 2012 Jan 7.

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

Author information

1
Department of Cellular Pathology, University Hospital of North Staffordshire, UK.

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 myofib rob lasts 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.

KEYWORDS:

Idiopathic Pulmonary Fibrosis; epithelial-mesenchymal transition; immunohistochemistry; prognostic markers; tissue repair and remodelling

PMID:
22295148
PMCID:
PMC3267487
[Indexed for MEDLINE]
Free PMC Article

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