You are here

  • Home
  • Online First
  • Unravelling switch/sucrose non-fermentable (SWI-SNF) complex-deficient thoracic tumours: a clinicopathological comparative on undifferentiated tumours and non-small cell lung carcinomas with BRG1 and BRM deficiency

Article Text

Article menu
Download PDFPDF
Original research
Unravelling switch/sucrose non-fermentable (SWI-SNF) complex-deficient thoracic tumours: a clinicopathological comparative on undifferentiated tumours and non-small cell lung carcinomas with BRG1 and BRM deficiency
  1. Ridhi Sood1,
  2. Arshi Tandon1,
  3. Warisa Khatoon1,
  4. Jayashimman Vasanthraman2,
  5. Aruna Nambirajan1,
  6. Anant Mohan3,
  7. Prabhat Singh Malik4,
  8. Deepali Jain1
  1. 1Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
  2. 2AIIMS, New Delhi, India
  3. 3Pulmonary, Critical care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
  4. 4Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
  1. Correspondence to Dr Deepali Jain; deepalijain76{at}aiims.edu

Abstract

Aims This study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cell lung carcinomas (SWI/SNF-dNSCLC) and to address cases with intermediate features.

Methods The pathology department archive was searched for all primary mediastinal, pleural and lung-based malignancies that showed aberrant expression of two SWI/SNF proteins the Brahma (BRM) aka SMARCA2 and/or (Brahma-related gene 1 (BRG1) aka SMARCA4. Patient demographics, treatment and clinical outcomes were collected from records and telephonic interviews. Differences in histopathological features and immunohistochemical stains were analysed. Cases with characteristics intermediate between both tumour entities were sequenced to advance our understanding of their biology and to assign them a more accurate classification.

Results We identified 50 tumours with SMARCA4 and/or SMARCA2 deficiencies, including 23 (46%) SMARCA4-dUT, 18 (36%) SMARCA4-dNSCLC and 2 (4%) SMARCA2-dNSCLC. Dyscohesive or undifferentiated cellular morphology versus frank gland formation along with keratin, claudin-4 and expression of >1 stem cell marker helped classify the SWI/SNF deficient tumours as SMARCA4-dUT or SWI/SNF-dNSCLC (p<0.05). Seven (14%) cases with BRG1 deficiency displayed ‘intermediate’ features of both SMARCA4-dNSCLC and SMARCA4-dUT and had the shortest overall survival. The smoking-related gene signature was observed on sequencing in all four cases examined.

Conclusion Tumours with intermediate features between SMARCA4-dUT and SWI/SNF-dNSCLC exist and portend an equally poor prognoses. Immunostains, including keratin, claudin-4, TTF1, HepPar1, stem cell markers, along with BRG1 and BRM testing, are essential adjuncts to morphology, while molecular studies can offer supplementary evidence in challenging cases.

  • IMMUNOHISTOCHEMISTRY
  • Lung Neoplasms
  • Pathology, Molecular

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

https://doi.org/10.1136/jcp-2024-209619

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information.

    View Full Text

    Footnotes

    • Handling editor Runjan Chetty.

    • Presented at Part of the work presented as a poster in World Conference on Lung Cancer (WCLC), Singapore, 2023

    • Contributors RS: data analysis and interpretation, drafting the article, critical revision of the article. AT: data collection, data analysis and interpretation, drafting the article. WK: data collection and analysis. JV: data collection. AN: data collection and analysis. AM: data collection PSM: data collection. DJ: conception or design of the work, drafting the article, critical revision of the article. The guarantor of the work is DJ.

      .

    • Funding Indian Council of Medical Research (ICMR), Code: I1482.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; internally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.