Recurrent NAB2–STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas

Nicola Fusco, Elena Guerini-Rocco, Claudia Augello, Andrea Terrasi, Giulia Ercoli, Caterina Fumagalli, Davide Vacirca, Paola Braidotti, Antonina Parafioriti, Marta Jaconi, Letterio Runza, Vijayalakshmi Ananthanarayanan, Fabio Pagni, Silvano Bosari, Massimo Barberis, Stefano Ferrero

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aims: 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. Methods and 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.

Original languageEnglish
Pages (from-to)906-917
Number of pages12
JournalHistopathology
Volume70
Issue number6
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Adenofibroma
Gene Fusion
Estrogen Receptors
Lung
Solitary Fibrous Tumors
Cadherins
Exons
Epithelium
Keratin-7
Fibroadenoma
Respiratory Mucosa
Neoplasms
Mutation
Hamartoma
Androgen Receptors
Vimentin
Progesterone Receptors
Electron Microscopy
Breast

Keywords

  • E-cadherin
  • ER
  • fibroadenoma
  • immunohistochemistry
  • MED12
  • NAB2–STAT6
  • pulmonary adenofibroma
  • Sanger sequencing
  • solitary fibrous tumour

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Recurrent NAB2–STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas. / Fusco, Nicola; Guerini-Rocco, Elena; Augello, Claudia; Terrasi, Andrea; Ercoli, Giulia; Fumagalli, Caterina; Vacirca, Davide; Braidotti, Paola; Parafioriti, Antonina; Jaconi, Marta; Runza, Letterio; Ananthanarayanan, Vijayalakshmi; Pagni, Fabio; Bosari, Silvano; Barberis, Massimo; Ferrero, Stefano.

In: Histopathology, Vol. 70, No. 6, 01.05.2017, p. 906-917.

Research output: Contribution to journalArticle

Fusco, Nicola ; Guerini-Rocco, Elena ; Augello, Claudia ; Terrasi, Andrea ; Ercoli, Giulia ; Fumagalli, Caterina ; Vacirca, Davide ; Braidotti, Paola ; Parafioriti, Antonina ; Jaconi, Marta ; Runza, Letterio ; Ananthanarayanan, Vijayalakshmi ; Pagni, Fabio ; Bosari, Silvano ; Barberis, Massimo ; Ferrero, Stefano. / Recurrent NAB2–STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas. In: Histopathology. 2017 ; Vol. 70, No. 6. pp. 906-917.
@article{dea2f406cd9247b5b78223807b581435,
title = "Recurrent NAB2–STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas",
abstract = "Aims: 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. Methods and 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.",
keywords = "E-cadherin, ER, fibroadenoma, immunohistochemistry, MED12, NAB2–STAT6, pulmonary adenofibroma, Sanger sequencing, solitary fibrous tumour",
author = "Nicola Fusco and Elena Guerini-Rocco and Claudia Augello and Andrea Terrasi and Giulia Ercoli and Caterina Fumagalli and Davide Vacirca and Paola Braidotti and Antonina Parafioriti and Marta Jaconi and Letterio Runza and Vijayalakshmi Ananthanarayanan and Fabio Pagni and Silvano Bosari and Massimo Barberis and Stefano Ferrero",
year = "2017",
month = "5",
day = "1",
doi = "10.1111/his.13165",
language = "English",
volume = "70",
pages = "906--917",
journal = "Histopathology",
issn = "0309-0167",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Recurrent NAB2–STAT6 gene fusions and oestrogen receptor-α expression in pulmonary adenofibromas

AU - Fusco, Nicola

AU - Guerini-Rocco, Elena

AU - Augello, Claudia

AU - Terrasi, Andrea

AU - Ercoli, Giulia

AU - Fumagalli, Caterina

AU - Vacirca, Davide

AU - Braidotti, Paola

AU - Parafioriti, Antonina

AU - Jaconi, Marta

AU - Runza, Letterio

AU - Ananthanarayanan, Vijayalakshmi

AU - Pagni, Fabio

AU - Bosari, Silvano

AU - Barberis, Massimo

AU - Ferrero, Stefano

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Aims: 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. Methods and 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.

AB - Aims: 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. Methods and 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.

KW - E-cadherin

KW - ER

KW - fibroadenoma

KW - immunohistochemistry

KW - MED12

KW - NAB2–STAT6

KW - pulmonary adenofibroma

KW - Sanger sequencing

KW - solitary fibrous tumour

UR - http://www.scopus.com/inward/record.url?scp=85013663964&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013663964&partnerID=8YFLogxK

U2 - 10.1111/his.13165

DO - 10.1111/his.13165

M3 - Article

C2 - 28072477

AN - SCOPUS:85013663964

VL - 70

SP - 906

EP - 917

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 6

ER -