Human pathology · 2026
TRPS1 and GATA3 expression in BRG1/SMARCA4-deficient malignant neoplasms.
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Han Jing, Ding Yang, Gan Qiong, Sweeney Keith, Huang Xiao, Hameed Nadia, Weissferdt Annikka, Wang Yaohong, Peng Yan, Sun Hongxia
Аннотация
OBJECTIVES: SMARCA4/BRG1-deficient malignant neoplasms are rare, high-grade tumors originating in sinonasal tract, thorax, gastrointestinal, and gynecological tracts, with breast-origin cases being underexplored. In this study, we aimed to investigate the pathologic features of BRG1-deficient breast carcinoma. We also assessed the diagnostic utility of TRPS1 and GATA3 immunohistochemical staining in identifying BRG1-deficient breast carcinomas and distinguishing them from BRG1-deficient tumors of other primary sites.
METHODS: To identify BRG1-deficient breast and non-breast cases, we detected BRG1 expression in 408 breast carcinomas using tissue microarrays. We also searched the institutional database for BRG1-deficient malignant neoplasms of both breast and non-breast origins diagnosed between 2021 and 2025. In total, we identified 22 cases from breast/axilla (n = 5), thoracic (n = 8), gastrointestinal (n = 5), and gynecologic (n = 4) sites. We then investigated the pathological features of BRG1-deficient breast carcinomas. We also assessed TRPS1 and GATA3 immunohistochemical staining in these BRG1-deficient tumors of different primary sites.
RESULTS: Only 1 breast carcinoma showed BRG1 loss among the 408 cases in tissue microarray. BRG1-deficient breast carcinomas are high-grade tumors with primitive morphology. All the 5 cases had TRPS1 positivity, with 3 also positive for GATA3. In contrast, no tumors of the 17 BRG1-deficient thoracic, gastrointestinal, or gynecologic origins exhibited co-expression of TRPS1 and GATA3, only 4 cases expressed either TRPS1 or GATA3 (most weakly).
CONCLUSIONS: This study confirmed that BRG1 loss is a rare event in breast carcinoma. Co-expression of TRPS1 and GATA3 is highly specific for breast origin in BRG1-deficient neoplasms. Combined use of these markers may aid in accurate tumor classification, particularly in metastatic or poorly differentiated presentations.
METHODS: To identify BRG1-deficient breast and non-breast cases, we detected BRG1 expression in 408 breast carcinomas using tissue microarrays. We also searched the institutional database for BRG1-deficient malignant neoplasms of both breast and non-breast origins diagnosed between 2021 and 2025. In total, we identified 22 cases from breast/axilla (n = 5), thoracic (n = 8), gastrointestinal (n = 5), and gynecologic (n = 4) sites. We then investigated the pathological features of BRG1-deficient breast carcinomas. We also assessed TRPS1 and GATA3 immunohistochemical staining in these BRG1-deficient tumors of different primary sites.
RESULTS: Only 1 breast carcinoma showed BRG1 loss among the 408 cases in tissue microarray. BRG1-deficient breast carcinomas are high-grade tumors with primitive morphology. All the 5 cases had TRPS1 positivity, with 3 also positive for GATA3. In contrast, no tumors of the 17 BRG1-deficient thoracic, gastrointestinal, or gynecologic origins exhibited co-expression of TRPS1 and GATA3, only 4 cases expressed either TRPS1 or GATA3 (most weakly).
CONCLUSIONS: This study confirmed that BRG1 loss is a rare event in breast carcinoma. Co-expression of TRPS1 and GATA3 is highly specific for breast origin in BRG1-deficient neoplasms. Combined use of these markers may aid in accurate tumor classification, particularly in metastatic or poorly differentiated presentations.