Serpin B4 isoform overexpression is associated with aberrant epithelial proliferation and lung cancer in idiopathic pulmonary fibrosis.

Abstract:

AIMS:The aim of the study was to evaluate the role of Serpin B3/B4 in advanced idiopathic pulmonary fibrosis (IPF) patients, mainly focusing on epithelial proliferation. METHODS:Lungs from 48 IPF patients (including cases with cancer or high-grade epithelial dysplasia) were studied and compared with other diffuse parenchymal diseases and normal lungs. Immunohistochemistry for Serpin B3/B4 and Ki-67 was quantified in all cases, distinguishing stained metaplastic cells. In IPF patients correlations between Serpin expression and several clinicopathological data, including fibrotic remodelling [fibrosis extension and transforming growth factor β expression (TGF-β)] were performed. Molecular analysis was used for Serpin isoform characterisation. RESULTS:In IPF patients Serpin B3/B4 and Ki-67 were significantly overexpressed in many metaplastic cells (mainly squamous type) compared to control cases. Higher Serpin B3/B4 was found in older patients and cases with more impaired respiratory function. Serpin B3/B4 expression was related to both TGF-β and Ki-67 and was higher in patients with cancer/high-grade dysplasia. Serpin B3 was expressed in all cases, whereas Serpin B4 was expressed only in IPF. CONCLUSIONS:Serpin B3/B4, particularly Serpin B4, appears to play an important role in aberrant epithelial proliferation. Evaluation of Serpin B3/B4 could have prognostic value in predicting disease progression, especially in patients with increased susceptibility to lung cancer.

journal_name

Pathology

journal_title

Pathology

authors

Calabrese F,Lunardi F,Balestro E,Marulli G,Perissinotto E,Loy M,Nannini N,Valente M,Saetta M,Agostini C,Rea F

doi

10.1097/PAT.0b013e3283511b61

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

192-8

issue

3

eissn

0031-3025

issn

1465-3931

journal_volume

44

pub_type

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