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Updated: Aug 27, 2025

Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Analysis of SMARCA4 and SMARCA2 Loss in Lung Sarcomatoid Carcinomas
Halide Nur Urer1, Nurcan Unver, Neslihan Fener
1Department of Pathology, University of Health Sciences Turkey, Haseki Training and Research Hospital, ISTANBUL, TURKEY.
Objective:
Sarcomatoid carcinomas of the lung are a group of aggressive tumors. It has been reported that losses of SMARCA4 and SMARCA2, which play a role in the repair and remodeling of chromatin, contribute to the initiation, progression, and differentiation of neoplasms. The aim of our study was to examine SMARCA4 and SMARCA2 profiles in sarcomatoid carcinomas of the lung.
Material And Method:
We screened pleomorphic carcinomas (PCs), carcinosarcomas (CSs), and pulmonary blastomas (PBs). The loss of SMARCA4 and SMARCA2 expression in the tumors was evaluated using immunohistochemical methods. The tumors were also examined to determine immunophenotype, histological tumor diagnosis, surgical resection, tumor histological component, largest tumor diameter, and lymph node metastasis status.
Results:
Sixty-nine cases were screened, of which 84% were PCs, 13% were CSs, and 2.8% were PBs. In PCs components, 84.4% were biphasic and 15.5% were monophasic. The PCs showed the most frequent loss of SMARCA4 (25.8%) and SMARCA2 (44.8%). A loss of SMARCA4 and SMARCA2, respectively, was detected in 14.2% and 24.4% in both components of biphasic PCs; 12.2% and 14.2% in the sarcoma component of biphasic PCs; 0% and 8.1% in the carcinoma component of biphasic PCs; 22.2% and 33.3% in monophasic PCs; 0% and 22.2% in both components of CSs; and 0% and 22.2% in the sarcoma component of CSs.
Conclusion:
These findings demonstrate a loss of expression of SMARCA4 and SMARCA2 in pulmonary sarcomatoid carcinomas. Loss of the SMARCA complex may be caused by the heterogeneous morphological profile of sarcomatoid carcinomas, independent of tumor histopathological parameters.
Insights
Loss of SMARCA4 and SMARCA2 expression is common in aggressive lung sarcomatoid carcinomas. This finding may be linked to the tumors' diverse cellular makeup, irrespective of specific histological features.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Sarcomatoid carcinomas of the lung are aggressive neoplasms.
- SMARCA4 and SMARCA2 are crucial for chromatin repair and remodeling, influencing tumor development.
- Loss of these proteins is implicated in various cancers.
Purpose of the Study:
- To investigate the expression profiles of SMARCA4 and SMARCA2 in pulmonary sarcomatoid carcinomas.
- To correlate these profiles with histological subtypes and tumor characteristics.
Main Methods:
- Immunohistochemical analysis of SMARCA4 and SMARCA2 expression.
- Screening of pleomorphic carcinomas, carcinosarcomas, and pulmonary blastomas.
- Evaluation of tumor immunophenotype, histology, and metastasis status.
Main Results:
- Sixty-nine cases were analyzed, predominantly pleomorphic carcinomas (84%).
- Loss of SMARCA4 was observed in 25.8% and SMARCA2 in 44.8% of pleomorphic carcinomas.
- Expression loss varied across tumor components and subtypes, with higher rates in monophasic pleomorphic carcinomas and carcinosarcomas.
Conclusions:
- A significant loss of SMARCA4 and SMARCA2 expression occurs in lung sarcomatoid carcinomas.
- This loss appears independent of tumor histopathological parameters.
- The heterogeneous nature of these tumors may contribute to SMARCA complex dysregulation.

