Science and Research

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

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.

  • Herpel, E.
  • Rieker, R. J.
  • Dienemann, H.
  • Muley, T.
  • Meister, M.
  • Hartmann, A.
  • Warth, A.
  • Agaimy, A.

Keywords

  • Adenocarcinoma/genetics/pathology
  • 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
  • *Adenocarcinoma
  • *Nsclc
  • *Smarca2
  • *Smarca4
  • *SWI/SNF complex
  • *Squamous cell carcinoma
Publication details
DOI: 10.1016/j.anndiagpath.2016.10.006
Journal: Ann Diagn Pathol
Pages: 47-51 
Work Type: Original
Location: TLRC
Disease Area: LC
Partner / Member: RKU, Thorax
Access-Number: 28038711
See publication on PubMed

DZL Engagements

chevron-down