A subset of thoracic SMARCA4-deficient undifferentiated tumors express GATA3 Journal Article
| Authors: | Coconubo, D. M.; Wangsiricharoen, S.; Pettus, J. R.; Linos, K.; Pinto, A.; Wang, W. L.; Kerr, D. A.; Cloutier, J. M. |
| Article Title: | A subset of thoracic SMARCA4-deficient undifferentiated tumors express GATA3 |
| Abstract: | Introduction : Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare and highly aggressive malignant neoplasm characterized by high-grade undifferentiated morphologic features and recurrent inactivating mutations of SMARCA4. These tumors consistently exhibit loss of SMARCA4 (BRG1) while displaying variable expression of other nonspecific markers. Recently, we encountered a SMARCA4-UT demonstrating immunoreactivity for GATA3, and we sought to characterize this phenomenon in a larger series. Methods : A total of nine SMARCA4-UTs were examined from 3 large academic institutions. The clinicopathologic and molecular characteristics were studied and GATA3 immunohistochemistry was performed. Results : The cohort included 5 male and 4 female patients, with a median age of 54 years and a median smoking history of 37 pack-years. At initial diagnosis, mediastinal lymph node involvement was observed in 5 patients (56%) while distant metastases were present in 7 patients (78%). The median survival was 6 months. Histologically, the tumors were characterized by sheets of undifferentiated epithelioid and/or rhabdoid cells, accompanied by frequent mitotic figures and necrosis. Immunohistochemically, all tumors displayed a complete loss of BRG1 expression. Notably, 4 of 9 tumors (44%) were positive for GATA3 expression, including one tumor that exhibited strong and diffuse immunoreactivity. Conclusions : GATA3 expression in SMARCA4-UT may pose diagnostic challenges, requiring differentiation from other GATA3-positive tumors. This distinction is crucial for accurate prognostication and treatment decisions. © The Author(s) 2023. |
| Keywords: | immunohistochemistry; adult; cancer survival; clinical article; controlled study; human tissue; protein expression; aged; middle aged; gene mutation; genetics; clinical feature; histopathology; cancer patient; follow up; mitosis; metabolism; cd34 antigen; stem cell factor receptor; transcription factor gata 3; gene expression; tumor volume; nuclear protein; protein depletion; cohort analysis; smoking; transcription factor; pathology; immunoreactivity; protein p53; tumor marker; inflammatory cell; distant metastasis; transcription factors; nuclear proteins; thoracic neoplasms; endothelium cell; spindle cell; protein s 100; mitosis rate; cyclin dependent kinase inhibitor 2a; transcription factor fli 1; transcription factor sox2; myeloid differentiation factor 88; nonsense mutation; dna helicases; dna helicase; calretinin; cd99 antigen; notch1 receptor; cytokeratin ae1; cytokeratin ae3; mediastinum lymph node; cytokeratin 18; cytokeratin 8; synaptophysin; keratin; tumor necrosis; gata3; cell inclusion; brg1 protein; brg1; swi/snf; high throughput sequencing; gata3 transcription factor; dna sequencing; humans; human; male; female; article; median survival time; smarca4; biomarkers, tumor; smarca4 protein, human; homeobox protein nkx 2.1; platelet endothelial cell adhesion molecule 1; epithelioid histiocyte; thoracic smarca4 deficient undifferentiated tumor; thoracic tumor; undifferentiated thoracic tumor; gata3 protein, human |
| Journal Title: | International Journal of Surgical Pathology |
| Volume: | 32 |
| Issue: | 4 |
| ISSN: | 1066-8969 |
| Publisher: | Sage Publications |
| Date Published: | 2024-06-01 |
| Start Page: | 684 |
| End Page: | 691 |
| Language: | English |
| DOI: | 10.1177/10668969231188904 |
| PUBMED: | 37461275 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
