{"title":"Clinicopathological characterization of Switch/Sucrose-non-fermentable (Swi/Snf) complex (ARID1A, SMARCA2, SMARCA4)-deficient endocervical adenocarcinoma.","authors":"Chao Cao, Zi-Yun Wu, Wei Liao, Li-Jun Wei, Hao-Yu Liang, Xia Yang, Rong-Zhen Luo, Li-Li Liu","doi":"10.1186/s12935-025-03794-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Subunits of the Switch/Sucrose-non-fermentable (Swi/Snf) complex, such as ARID1A, SMARCA4, SMARCA2, etc., have been implicated in the development of gynecologic cancers. However, their prevalence and clinical implications in endocervical adenocarcinoma (ECA) remain unclear. This study aimed to evaluate the expression of Swi/Snf complex subunits in ECA and characterize the clinicopathological and immune microenvironment features of Swi/Snf-deficient ECA.</p><p><strong>Methods: </strong>We evaluated 604 ECA using representative tissue microarrays, collected clinicopathologic data, reviewed histological features, and performed immunohistochemical staining for several Swi/Snf complex subunits, mismatch repair (MMR), immune cell markers, and immune checkpoint ligands proteins.</p><p><strong>Results: </strong>Among the 604 cases examined, five Swi/Snf subunit expression patterns were identified, including intact expression, deficient expression, 'checkerboard' expression, reduced expression, and heterogeneous expression. Deficiencies of ARID1A (3.97%, 24/604), SMARCA2 (2.32%,14/604), and SMARCA4 (1.49%, 9/604) were observed. Defining Swi/Snf deficiency as loss of any subunit, the overall deficiency rate was 5.96% (36/604). Swi/Snf-deficient ECA tended to advanced FIGO stage (III-IV, P = 0.041), larger tumor size (P < 0.001), deeper stromal invasion (≥ 1/3, P = 0.046), and higher lymph node metastasis rate (P = 0.037). Morphologically, Swi/Snf-deficient ECA displayed frequent poor differentiation (P = 0.001), medullary features (P < 0.001), high nuclear grade (P < 0.001), necrosis (P = 0.001), stromal tumor-infiltrating lymphocytes (sTILs, P < 0.001), peritumoral lymphocyte aggregation (P = 0.001), and tertiary lymphoid structures (TLS, P < 0.001). Immune subset analysis revealed significantly elevated densities of CD3⁺ T cells, CD8⁺ T cells, CD38⁺ plasma cells, CD56⁺ NK cells, CD68⁺ macrophages, and PD-1⁺ T cells in Swi/Snf-deficient ECA (P < 0.05). Swi/Snf-deficient ECA demonstrated higher PD-L1 combined positive score (CPS) positivity (P < 0.001), and was more frequently associated with mismatch repair deficiency (MMRD, P < 0.001). Survival analysis indicated shorter overall survival (median: 53 vs. 64.5 months, P = 0.0307) and disease-free survival (median: 52 vs. 60.5 months, P = 0.0228) in Swi/Snf-deficient ECA patients.</p><p><strong>Conclusions: </strong>Swi/Snf complex deficiency is rare but significantly associated with NHPVA, aggressive pathological features, immunologically activated phenotypes, and MMRD. Swi/Snf status evaluation may inform novel therapeutic strategies for ECA patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"170"},"PeriodicalIF":6.0000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042307/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03794-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Subunits of the Switch/Sucrose-non-fermentable (Swi/Snf) complex, such as ARID1A, SMARCA4, SMARCA2, etc., have been implicated in the development of gynecologic cancers. However, their prevalence and clinical implications in endocervical adenocarcinoma (ECA) remain unclear. This study aimed to evaluate the expression of Swi/Snf complex subunits in ECA and characterize the clinicopathological and immune microenvironment features of Swi/Snf-deficient ECA.
Methods: We evaluated 604 ECA using representative tissue microarrays, collected clinicopathologic data, reviewed histological features, and performed immunohistochemical staining for several Swi/Snf complex subunits, mismatch repair (MMR), immune cell markers, and immune checkpoint ligands proteins.
Results: Among the 604 cases examined, five Swi/Snf subunit expression patterns were identified, including intact expression, deficient expression, 'checkerboard' expression, reduced expression, and heterogeneous expression. Deficiencies of ARID1A (3.97%, 24/604), SMARCA2 (2.32%,14/604), and SMARCA4 (1.49%, 9/604) were observed. Defining Swi/Snf deficiency as loss of any subunit, the overall deficiency rate was 5.96% (36/604). Swi/Snf-deficient ECA tended to advanced FIGO stage (III-IV, P = 0.041), larger tumor size (P < 0.001), deeper stromal invasion (≥ 1/3, P = 0.046), and higher lymph node metastasis rate (P = 0.037). Morphologically, Swi/Snf-deficient ECA displayed frequent poor differentiation (P = 0.001), medullary features (P < 0.001), high nuclear grade (P < 0.001), necrosis (P = 0.001), stromal tumor-infiltrating lymphocytes (sTILs, P < 0.001), peritumoral lymphocyte aggregation (P = 0.001), and tertiary lymphoid structures (TLS, P < 0.001). Immune subset analysis revealed significantly elevated densities of CD3⁺ T cells, CD8⁺ T cells, CD38⁺ plasma cells, CD56⁺ NK cells, CD68⁺ macrophages, and PD-1⁺ T cells in Swi/Snf-deficient ECA (P < 0.05). Swi/Snf-deficient ECA demonstrated higher PD-L1 combined positive score (CPS) positivity (P < 0.001), and was more frequently associated with mismatch repair deficiency (MMRD, P < 0.001). Survival analysis indicated shorter overall survival (median: 53 vs. 64.5 months, P = 0.0307) and disease-free survival (median: 52 vs. 60.5 months, P = 0.0228) in Swi/Snf-deficient ECA patients.
Conclusions: Swi/Snf complex deficiency is rare but significantly associated with NHPVA, aggressive pathological features, immunologically activated phenotypes, and MMRD. Swi/Snf status evaluation may inform novel therapeutic strategies for ECA patients.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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