title: Serpin B4 isoform overexpression is associated with aberrant epithelial proliferation and lung cancer in idiopathic pulmonary fibrosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. fiorella.calabrese@unipd.it
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Balestro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marulli
authors.forename: Egle
authors.initials: E
authors.lastname: Perissinotto
authors.forename: Monica
authors.initials: M
authors.lastname: Loy
authors.forename: Nazarena
authors.initials: N
authors.lastname: Nannini
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Marina
authors.initials: M
authors.lastname: Saetta
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D015843:Serpins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019394:Ki-67 Antigen; D020033:Protein Isoforms; D015843:Serpins; D016212:Transforming Growth Factor beta; C051072:squamous cell carcinoma-related antigen