Immunohistochemical expression of embryonic stem cell markers in malignant rhabdoid tumors.
ABSTRACT Malignant rhabdoid tumor is a highly aggressive pediatric neoplasm molecularly characterized by inactivating mutations of the SMARCB1 gene, a potent tumor suppressor and member of the SWI/SNF chromatin remodeling complex. It has been suggested that oncogenesis in SMARCB1-deficient cancers, such as malignant rhabdoid tumors, is driven not by the loss of SWI/SNF function but by an aberrant functioning of the BRG1-containing SWI/SNF complex. Since Brg1 is required for self-renewal and pluripotency of mouse embryonic stem cells, we hypothesized that the human malignant rhabdoid tumors may express pluripotency genes such as SALL4 , LIN28 , OCT3 and OCT4 (OCT3/4) , NANOG , and TCL1 . To test this hypothesis, we studied the immunohistochemical expression of SALL4, LIN28, OCT3/4, NANOG, and TCL1 in 11 malignant rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumors) and 5 malignant rhabdoid tumors of the kidney. Of the 16 malignant rhabdoid tumors, 14 (88%) tumors showed robust SALL4 and/or LIN28 expression. No tumor showed any significant OCT3/4, NANOG, or TCL1 expression. Our results suggest that malignant rhabdoid tumors may arise from and/or share features with embryonic stem cells or germ cells.
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ABSTRACT: Link is: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3078Oncotarget 12/2014; · 6.63 Impact Factor
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ABSTRACT: Malignant mixed Mullerian tumor (MMMT) is an uncommon aggressive neoplasm composed of both malignant epithelial and mesenchymal components. In this study, immunohistochemical stains of germ cell markers, including SALL4, OCT3/4, glypican-3, and alpha-fetal protein (AFP), and CDX2 were performed in a series of MMMTs. SALL4 nuclear immunoreactivity was detected in 6 out of 19 cases (33%). The staining extent ranged from focal to extensive. The staining intensity was usually intermediate to strong (the score ranged from 1.5 to 3, and average score was 2.3 ± 0.5 in the positive cases). In addition, glypican-3 cytoplasmic reactivity was detected in 14 out of 16 cases (88%) with a mean score of 1.8 ± 0.7 (score ranging from 1 to 3). In contrast, OCT3/4 was only positive in 1 out of 19 cases and AFP in 2 out of 18 cases (11%). In summary, SALL4 and glypican-3 were frequently expressed in a subset of MMMTs. Their roles in the pathogenesis and biology of MMMT are yet to be determined. MMMT should be included in the differential diagnosis when a tumor is positive for SALL4 and/or glypican-3.07/2012; 2012:569609. DOI:10.1155/2012/569609
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ABSTRACT: AimsMalignant rhabdoid tumours (MRTs) and epithelioid sarcomas (ESs) are distinctive malignant neoplasms with characteristic clinicopathologic features. However, these 2 tumour types share some phenotypes such as epithelioid/rhabdoid cytology, expression of epithelial markers, and immunohistochemical loss of INI1. The distinction can be problematic in atypical clinical settings, and ancillary diagnostic tools are needed. The expression of CD34 is widely cited to favor the diagnosis of ESs, but no formal comparative study has been performed in the post-INI1 era. Here, we evaluated the utility of SALL4 for differentiating MRTs from ESs and compared its performance to that of CD34.Methods and resultsFifteen MRTs and 36 ESs were retrieved. All MRTs and ESs lacked INI1 reactivity, except for 1 MRT that lacked BRG1. A representative slide from each case was stained using antibodies against SALL4 and CD34. Ten (67%) of 15 MRTs expressed SALL4. In contrast, only 1 (3%) of the 36 ES cases was SALL4 positive. CD34 staining was observed in 9 (60%) of 15 MRTs and 29 (81%) of 36 ESs.Conclusions Despite moderate sensitivity, SALL4 expression may aid in distinguishing MRTs from ESs. CD34 was found to have questionable utility in making such distinctions.This article is protected by copyright. All rights reserved.Histopathology 05/2014; 66(2). DOI:10.1111/his.12460 · 3.30 Impact Factor