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

• Published in: Pathology 2012-04, Vol.44 (3), p.192-198
• Main Authors: Calabrese, Fiorella, Lunardi, Francesca, Balestro, Elisabetta, Marulli, Giuseppe, Perissinotto, Egle, Loy, Monica, Nannini, Nazarena, Valente, Marialuisa, Saetta, Marina, Agostini, Carlo, Rea, Federico
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, Neoplasm - metabolism; Carcinoma in Situ - complications; Carcinoma in Situ - diagnosis; Carcinoma in Situ - metabolism; Cell Proliferation; Female; Humans; Idiopathic pulmonary fibrosis; Idiopathic Pulmonary Fibrosis - complications; Idiopathic Pulmonary Fibrosis - diagnosis; Idiopathic Pulmonary Fibrosis - metabolism; Ki-67 Antigen - metabolism; lung cancer; Lung Neoplasms - complications; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Lung Transplantation; Male; Middle Aged; Prognosis; proliferation; Protein Isoforms; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; serpin B3/B4; Serpins - metabolism; Transforming Growth Factor beta - metabolism
• ISSN: 0031-3025; 1465-3931
• DOI: 10.1097/PAT.0b013e3283511b61

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. 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. 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 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.