SMARCA4 and SMARCA2 deficiency in non-small cell lung cancer: immunohistochemical survey of 316 consecutive specimens.

Abstract

The chromatin remodeling switch sucrose nonfermentable (SWI/SNF) complex has been increasingly implicated in the pathogenesis and dedifferentiation of neoplasms from several organs with prognostic and potential therapeutic implications. We herein investigated the expression of the SWI/SNF complex catalytic subunits SMARCA4 (BRG1) and SMARCA2 (BRM) in 316 consecutive non-small cell lung cancer (NSCLC) specimens on tissue microarrays (171 adenocarcinomas [ADCAs], 130 squamous cell carcinomas [SCCs], 9 adenosquamous carcinomas, and 6 large cell carcinomas) excluding undifferentiated/giant cell or rhabdoid carcinomas. Complete loss of SMARCA4 was observed in 8 (5.5%) of 146 evaluable pulmonary ADCAs and 6 (5.2%) of 115 evaluable pulmonary SCCs, whereas 9 (6.4%) of 140 ADCAs and 2 (1.7%) of 117 SCCs showed SMARCA2 loss. Two of 6 large cell carcinomas were SMARCA2 deficient. Concurrent loss of both markers was observed in 4 cases (2 ADCAs and 2 SCCs). Of 15 ADCAs with loss of either or both markers, 12 (80%) were TTF1 negative. In conclusion, SMARCA4 and SMARCA2 deficiency is observed in 5.1% and 4.8% of NSCLC, respectively. SMARCB1 expression was intact in all cases. The presence of differentiated histology (glandular or squamous) is a novel aspect among SWI/SNF-deficient carcinomas which in other organs generally are associated with undifferentiated/rhabdoid morphology. The predominance of TTF1 negativity among SWI/SNF-deficient pulmonary ADCA (80%) underlines the need to include these 2 markers in the evaluation of TTF1-negative ADCA of putative pulmonary origin. Given the recently documented potential of SMARCA4 loss as a predictor of chemosensitivity to platinum-based chemotherapy in NSCLC, recognition of the clinicopathological features of SMARCA4-deficient NSCLC in routine surgical pathology practice is recommended.

• Authors: Esther Herpel, Ralf J Rieker, Hendrik Dienemann, Thomas Muley, Michael Meister, Arndt Hartmann, Arne Warth, Abbas Agaimy
• Journal: Annals of diagnostic pathology (Ann Diagn Pathol) Vol. 26 Pg. 47-51 (Feb 2017) ISSN: 1532-8198 [Electronic] United States
• PMID: 28038711 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• Nuclear Proteins
• SMARCA2 protein, human
• Transcription Factors
• SMARCA4 protein, human
• DNA Helicases

Topics

• Adenocarcinoma (genetics, pathology)
• Adenocarcinoma of Lung
• Aged
• Aged, 80 and over
• Carcinoma, Large Cell (pathology)
• Carcinoma, Non-Small-Cell Lung (genetics, pathology)
• Carcinoma, Squamous Cell (pathology)
• Cell Differentiation (physiology)
• Chromosomal Proteins, Non-Histone (genetics)
• DNA Helicases (deficiency)
• DNA-Binding Proteins (metabolism)
• Female
• Humans
• Lung Neoplasms (genetics, pathology)
• Male
• Middle Aged
• Mutation (genetics)
• Nuclear Proteins (deficiency)
• Transcription Factors (deficiency)