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

doi:10.1097/PAT.0b013e3283511b61

Pathology

Volume 44, Issue 3, April 2012, Pages 192-198

https://doi.org/10.1097/PAT.0b013e3283511b61 Get rights and content

Summary

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.

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

Summary

Aims

Methods

Results

Conclusions

Am J Med

Mayo Clin Proc

Mod Pathol

Anal Biochem

Pathol Res Pract

Hum Pathol

Exp Mol Pathol

Lab Invest

Lab Invest

J Biol Chem

J Heart Lung Transplant

P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis

Am J Respir Crit Care Med

Idiopathic pulmonary fibrosis and malignancy

Curr Opin Pulm Med

Lung cancer in patients with idiopathic pulmonary fibrosis

Eur Respir J

Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis

Cancer

Relationship of interstitial pneumonia honeycombing and atypical epithelial proliferation to cancer of the lung

Cancer

Pulmonary fibrosis and lung carcinoma: a comparative study of metaplastic epithelia in honeycombed areas of usual interstitial pneumonia with or without lung carcinoma

Pathol Int

Overexpression of squamous cell carcinoma antigen in idiopathic pulmonary fibrosis: clinicopatho- logical correlations

Thorax

Cross-class inhibition of the cysteine proteinases cathepsins K. L, and S by the Serpin squamous cell carcinoma antigen 1: a kinetic analysis

Biochemistry

Suppression of a squamous cell carcinoma (SCC)-related Serpin, SCC antigen, inhibits tumor growth with increased intratumor infiltration of natural killer cells

Cancer Res