title: Recurrent NAB2-STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas.
abstract: OBJECTIVE
  Pulmonary adenofibromas are rare benign fibroepithelial tumours of the lung with unknown histogenesis and an indolent clinical behaviour. Their stroma resembles that of solitary fibrous tumours, whereas the glands are composed of respiratory epithelium organized in a phyllodes-like architecture. Differentiation of pulmonary adenofibromas from other more aggressive intrathoracic tumours is clinically relevant. However, their biology is unknown. Here, we sought to characterize pulmonary adenofibromas at a clinicopathological level and to define whether they could be underpinned by a highly recurrent somatic genetic alteration akin to tumours with similar morphology.
  
  
  RESULTS
  Seven pulmonary adenofibromas were subjected to immunohistochemical analysis for thyroid transcription factor 1 (TTF1), napsin A, cytokeratin 7, E-cadherin, CD99, CD34, CD31, STAT6, oestrogen receptor (ER), progesterone receptor, androgen receptor, bcl-2, and vimentin, as well as electron microscopy and capillary sequencing on microdissected samples to evaluate the presence of NAB2-STAT6 fusion genes and MED12 exon 2 mutations in their discrete components. A control group comprising pulmonary solitary fibrous tumours, pulmonary hamartomas and breast fibroadenomas was also analysed. We confirmed that the stromal elements of pulmonary adenofibromas pertain to the fibroblastic lineage, and show ER overexpression in 71% of cases, whereas the epithelium consists of TTF1-positive, E-cadherin positive bronchiolar elements. A highly recurrent NAB2-STAT6 fusion variant (exon 4-exon 2) was detected in the stroma but not in the epithelium. No MED12 mutations were identified.
  
  
  CONCLUSIONS
  Here, we demonstrate that pulmonary adenofibromas are neoplastic lesions harbouring the molecular hallmark of solitary fibrous tumours.
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Nicola
authors.identifier: http://orcid.org/0000-0002-9101-9131
authors.initials: N
authors.lastname: Fusco
authors.affiliation: Division of Pathology, European Institute of Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Guerini-Rocco
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Augello
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Andrea
authors.identifier: http://orcid.org/0000-0003-4955-3346
authors.initials: A
authors.lastname: Terrasi
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ercoli
authors.affiliation: Division of Pathology, European Institute of Oncology, Milan, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fumagalli
authors.affiliation: Division of Pathology, European Institute of Oncology, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vacirca
authors.affiliation: Division of Pathology, San Paolo Hospital, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Braidotti
authors.affiliation: Department of Pathology, Orthopaedic Institute Gaetano Pini, Milan, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Parafioriti
authors.affiliation: School of Pathology, University of Milan, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Jaconi
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Letterio
authors.initials: L
authors.lastname: Runza
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, Chicago, IL, USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Ananthanarayanan
authors.affiliation: Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pagni
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.affiliation: Division of Pathology, European Institute of Oncology, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
mesh_terms: D000232:Adenofibroma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; C491000:NAB2 protein, human; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human
keywords: 
  ER
  ; 
  MED12
  ; 
  NAB2-STAT6
  ; E-cadherin; Sanger sequencing; fibroadenoma; immunohistochemistry; pulmonary adenofibroma; solitary fibrous tumour