Loss of expression of the SWI/SNF complex is a frequent event in undifferentiated/dedifferentiated urothelial carcinoma of the urinary tract
Language English Country Germany Media print-electronic
Document type Journal Article
PubMed
27339451
DOI
10.1007/s00428-016-1977-y
PII: 10.1007/s00428-016-1977-y
Knihovny.cz E-resources
- Keywords
- ARID1A, Renal pelvis, Rhabdoid carcinoma, SMARCA2, SMARCB1, SWI/SNF, Undifferentiated carcinoma, Urinary bladder, Urothelial carcinoma,
- MeSH
- DNA-Binding Proteins MeSH
- DNA Helicases metabolism MeSH
- Adult MeSH
- SMARCB1 Protein metabolism MeSH
- Immunohistochemistry methods MeSH
- Nuclear Proteins metabolism MeSH
- Carcinoma, Transitional Cell metabolism pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Urinary Tract metabolism pathology MeSH
- Rhabdoid Tumor diagnosis metabolism pathology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Transcription Factors metabolism MeSH
- Urologic Neoplasms diagnosis metabolism pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- ARID1A protein, human MeSH Browser
- DNA-Binding Proteins MeSH
- DNA Helicases MeSH
- SMARCB1 Protein MeSH
- Nuclear Proteins MeSH
- SMARCA2 protein, human MeSH Browser
- SMARCA4 protein, human MeSH Browser
- SMARCB1 protein, human MeSH Browser
- SMARCC1 protein, human MeSH Browser
- Transcription Factors MeSH
Loss of the SWI/SNF chromatin remodeling complex has been recently implicated in the pathogenesis of dedifferentiated carcinomas from different organs, but its possible role in undifferentiated urothelial carcinoma (UC) has not been studied to date. In this study, we analyzed by immunohistochemistry 14 undifferentiated UCs (11 from bladder and 3 from renal pelvis) with a nondescript anaplastic or rhabdoid morphology, using commercially available antibodies against the SWI/SNF components SMARCB1 (INI1), SMARCA2, SMARCA4, SMARCC1, SMARCC2, and ARID1A. Patients were eight females and six males aged 40 to 84 years (median, 65). All tumors were muscle-invasive (9 were T3-4). A conventional UC component was seen in eight cases and varied from in situ to papillary. The undifferentiated component comprised 60-100 % of the tumors. Histologically, most tumors showed diffuse dyscohesive or pseudoalveolar growth of variably sized cells with frequent rhabdoid features. Transition from conventional to undifferentiated UC was abrupt, except in one case. The undifferentiated component almost always expressed pan-cytokeratin AE1/AE3 (13/14) and variably vimentin (8/14) and GATA3 (9/14). Complete loss of at least one SWI/SNF subunit limited to the undifferentiated component was detected in 10/14 cases (71 %). SMARCA2 was most frequently lost (six) followed by ARID1A (four), SMARCB1/INI1 (two), SMARCA4 (one), and SMARCC1 (one). This is the first study exploring SWI/SNF expression in undifferentiated UC of the urinary tract. Our results are in line with recent studies reporting involvement of the SWI/SNF complex in the dedifferentiation process of a variety of epithelial neoplasms in different organs, including the urinary tract, and association with aggressive clinical course.
Department of Pathology Champalimaud Clinical Center Lisbon Portugal
Department of Urology and Pediatric Urology Saarland University Homburg Saar Germany
Department of Urology University Hospital of Erlangen Erlangen Germany
Indiana University School of Medicine Indianapolis IN 46202 USA
Sikl's Department of Pathology Charles University Medical Faculty Hospital Pilsen Czech Republic
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