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已发表论文
肺腺癌中 SMARCA2 缺失但保留 SMARCA4 并伴有β-连环蛋白异常表达
Authors Dai X , Feng X, Li J, Peng F
Received 11 April 2025
Accepted for publication 6 September 2025
Published 12 September 2025 Volume 2025:17 Pages 1961—1970
DOI https://doi.org/10.2147/CMAR.S533790
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 6
Editor who approved publication: Professor Bilikere Dwarakanath
Xiaomin Dai, Xiaoyue Feng, Jing Li, Fang Peng
Department of Pathology, Zhejiang Hospital, Hangzhou City, Zhejiang, People’s Republic of China
Correspondence: Fang Peng, Department of Pathology, Zhejiang Hospital, 12 Lingyin Road, Xihu District, Hangzhou City, Zhejiang, 310014, People’s Republic of China, Tel +86 13588881606, Email pengfang999@139.com
Background: The SWI/SNF complex is comprised of ATPase catalytic subunit SMARCA4/SMARCA2, evolutionarily conserved core subunits including SMARCB1, SMARCC1, and SMARCC2, as well as functionally specialized accessory subunits PBRM1 and ARID1A. Deletion or mutation of the catalytic subunit can lead to inactivation of the encoded protein and impaired overall function of the complex, contributing to tumorigenesis.
Methods: In this study, we conducted a retrospective analysis of seven cases of poorly differentiated lung adenocarcinoma from our institution that exhibited SMARCA2 deficiency while retaining SMARCA4 expression, and systematically evaluated the clinical characteristics, histological features, genetic alterations, and survival outcomes.
Results: Among the seven cases of SMARCA2-deficient lung adenocarcinoma, five were male and two were female, with an average age of 68.7 years. Four patients had a smoking history averaging 35 years, all seven patients exhibited respiratory symptoms. Histologically, these tumors displayed diverse features, including rhabdoid morphology, giant cells, and necrotic areas. The tumor cells exhibited eosinophilic cytoplasm, large nuclei with prominent nucleoli. Immunohistochemically, the tumor cells revealed SMARCA2 negativity with SMARCA4 expression. P53 staining revealed diffuse strong nuclear expression in 5 cases and complete absence expression in 2 cases. β-catenin expression was partially abnormal in 3 cases, with positive nuclear and cytoplasmic staining. PD-L1 expression was detected as positive in 5 cases. Next-generation sequencing identified mutations in driver genes KRAS, MET, and EGFR in 4 cases, and TP53 mutations in 7 cases. Clinical follow-up revealed that 2 patients died of tumor progression, 5 patients achieved complete response within a follow-up period of 10 to 33 months (median = 18.3 m).
Conclusion: SMARCA2-deficient with SMARCA4-preserved lung adenocarcinomas demonstrate substantial histological heterogeneity and may dedifferentiate into high-grade adenocarcinomas harboring TP53 mutations. In the assessment of poorly differentiated lung adenocarcinoma, immunohistochemical detection can identify this subtype for more precise clinical treatment strategies.
Keywords: lung adenocarcinoma, SMARCA2, SMARCA4, β-catenin, gene mutation
Department of Pathology, Zhejiang Hospital, Hangzhou City, Zhejiang, People’s Republic of China
Correspondence: Fang Peng, Department of Pathology, Zhejiang Hospital, 12 Lingyin Road, Xihu District, Hangzhou City, Zhejiang, 310014, People’s Republic of China, Tel +86 13588881606, Email pengfang999@139.com
Background: The SWI/SNF complex is comprised of ATPase catalytic subunit SMARCA4/SMARCA2, evolutionarily conserved core subunits including SMARCB1, SMARCC1, and SMARCC2, as well as functionally specialized accessory subunits PBRM1 and ARID1A. Deletion or mutation of the catalytic subunit can lead to inactivation of the encoded protein and impaired overall function of the complex, contributing to tumorigenesis.
Methods: In this study, we conducted a retrospective analysis of seven cases of poorly differentiated lung adenocarcinoma from our institution that exhibited SMARCA2 deficiency while retaining SMARCA4 expression, and systematically evaluated the clinical characteristics, histological features, genetic alterations, and survival outcomes.
Results: Among the seven cases of SMARCA2-deficient lung adenocarcinoma, five were male and two were female, with an average age of 68.7 years. Four patients had a smoking history averaging 35 years, all seven patients exhibited respiratory symptoms. Histologically, these tumors displayed diverse features, including rhabdoid morphology, giant cells, and necrotic areas. The tumor cells exhibited eosinophilic cytoplasm, large nuclei with prominent nucleoli. Immunohistochemically, the tumor cells revealed SMARCA2 negativity with SMARCA4 expression. P53 staining revealed diffuse strong nuclear expression in 5 cases and complete absence expression in 2 cases. β-catenin expression was partially abnormal in 3 cases, with positive nuclear and cytoplasmic staining. PD-L1 expression was detected as positive in 5 cases. Next-generation sequencing identified mutations in driver genes KRAS, MET, and EGFR in 4 cases, and TP53 mutations in 7 cases. Clinical follow-up revealed that 2 patients died of tumor progression, 5 patients achieved complete response within a follow-up period of 10 to 33 months (median = 18.3 m).
Conclusion: SMARCA2-deficient with SMARCA4-preserved lung adenocarcinomas demonstrate substantial histological heterogeneity and may dedifferentiate into high-grade adenocarcinomas harboring TP53 mutations. In the assessment of poorly differentiated lung adenocarcinoma, immunohistochemical detection can identify this subtype for more precise clinical treatment strategies.
Keywords: lung adenocarcinoma, SMARCA2, SMARCA4, β-catenin, gene mutation