ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor

doi:10.1016/j.humpath.2014.10.010

Human Pathology

Volume 46, Issue 2, February 2015, Pages 225-230

https://doi.org/10.1016/j.humpath.2014.10.010 Get rights and content

Summary

ERG is immunoexpressed in vascular endothelial tumors, blastic extramedullary myeloid tumors, and tumors with ERG-involved translocation, such as prostate carcinoma or Ewing sarcoma. Recently, ERG immunoexpression was reported in an epithelioid sarcoma, which is a SMARCB1/INI1-deficient tumor, although epithelioid sarcoma is not associated with chromosomal translocations involving ERG and is categorized as a tumor with uncertain differentiation. SALL4 is essential for a proliferation and stabilization of embryonic stem cells. It was reported that SALL4 expression may aid in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. We analyzed the frequency of ERG and SALL4 expressions in 80 SMARCB1/INI1-deficient tumors, including 45 epithelioid sarcomas (conventional-type, 24; proximal-type, 20), 17 malignant rhabdoid tumors, 5 atypical teratoid/rhabdoid tumors, 6 undifferentiated/unclassified sarcomas, 5 myoepithelial tumors, and 4 extraskeletal myxoid chondrosarcomas. We found that ERG expression was present in 18 of the epithelioid sarcomas (41%), including 13 conventional-type (54%) and 5 proximal-type (25%), whereas all 17 of the malignant rhabdoid tumors exhibited negative immunoreactivity. One atypical teratoid/rhabdoid tumor (20%), 1 myoepithelial carcinoma (20%), 1 undifferentiated/unclassified sarcoma (17%), and no extraskeletal myxoid chondrosarcomas (0%) also showed ERG expression. SALL4 expression was recognized in 5 epithelioid sarcomas (11%), 12 malignant rhabdoid tumors (71%), 2 atypical teradoid/rhabdoid tumors (40%), 4 undifferentiated/unclassified sarcomas (67%), 1 myoepithelial tumor (20%), and none of the extraskeletal myxoid chondrosarcomas (0%). Therefore, the evaluation of ERG and SALL4 immunoexpressions may be a useful diagnostic tool to distinguish epithelioid sarcoma, especially proximal type, from malignant rhabdoid tumor.

Introduction

The SMARCB1/INI1 gene is a member of the ATP-dependent SWI/SNF chromatin-remodeling complex and thus is a candidate for a tumor suppressor gene [1]. In a previous report, SMARCB1/INI1 immunohistochemical expression was not detected in any malignant rhabdoid tumor cases, and indeed, the absence of such expression was reported to be useful for the correct diagnosis of malignant rhabdoid tumor [2]. However, complete loss of SMARCB1/INI1 protein expression compared with normal cells of adjacent tissue has also been demonstrated in various tumors such as all renal medullary carcinomas, most epithelioid sarcomas, half of all epithelioid malignant peripheral nerve sheath tumors, approximately half of all pediatric myoepithelial carcinomas, and some extraskeletal myxoid chondrosarcomas [1], [3]. These SMARCB1/INI1-deficient tumors show a propensity for rhabdoid cytomorphology, and sometimes other overlapping immunohistochemical and histologic findings [1]. Therefore, differential diagnosis of these tumors is often difficult, and development of useful diagnostic tools is required.

Epithelioid sarcoma, which has been classified as a tumor of uncertain differentiation, has 2 histologic subtypes: a proximal “large cell” type and a classic or conventional “distal” type [4], [5]. Recently, it has been reported that epithelioid sarcoma can be labeled with antibodies to the N-terminus of ERG, which may cause diagnostic confusion for a vascular tumor or a tumor with ERG-involved translocation [6], [7], [8], and SALL4 expression may aid in distinguishing epithelioid sarcoma from malignant rhabdoid tumor [9]. However, ERG or SALL4 immunoexpression in the other SMARCB1/INI1-deficient tumors has never been evaluated.

In the present study, we analyzed immunohistochemical ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors, including epithelioid sarcomas. We also investigated the relation between ERG or SALL4 expression and various clinicopathological parameters and discussed the potential use of ERG or SALL4 expression as differential diagnostic tool.

Section snippets

Patients

SMARCB1/INI1-deficient tumors in the present study were selected from among more than 15 000 cases of bone and soft tissue tumors registered in the Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, between 1975 and 2013. The primary monoclonal antibody used in the case selection was BAF47, an antibody to the SMARCB1/INI1 gene product (clone 25, 1:250, 20-minute microwave; BD Transduction Laboratories, San Diego, CA). As a result of this

Results

Immunohistochemical results are summarized in Table 1. Thirteen (54%) of the 24 conventional-type and 5 (25%) of the 20 proximal-type epithelioid sarcoma cases were positive for ERG (Fig. 1A-D). ERG immunoreactivity was found significantly more frequently in conventional-type epithelioid sarcoma than in proximal-type epithelioid sarcoma (P = .048). On the other hand, all 17 of the malignant rhabdoid tumor cases were negative (Fig. 1E,F). ERG expression was also observed in 1 atypical

Discussion

ERG, which is a member of the erythroblast transformation-specific family of transcription factors, regulates endothelial cell differentiation, angiogenesis, and embryonic development [15]. Generally, ERG was immunoexpressed in vascular endothelial tumors, blastic extramedullary myeloid tumor, prostate carcinoma (which is associated with TMPRSS2-ERG fusion gene), and Ewing sarcoma (which is associated with EWSR1-ERG fusion gene) [6], [7], [15], [16], [17], [18]. In addition, although

Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research (B) (No. 25293088) and Scientific Research (C) (No. 26460435) from the Japan Society for the Promotion of Science, and for Clinical Research from the Ministry of Health Labour and Welfare, Tokyo, Japan. The English used in this article was revised by KN International (http://www.kninter.com/).

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Histopathology

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Citation Excerpt :
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^☆: Disclosures: The authors declare that there are no conflicts of interest to disclose.

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Original contributionERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor☆

Summary

Introduction

Section snippets

Patients

Results

Discussion

Acknowledgments

Hum Pathol

Mod Pathol

Int J Biochem Cell Biol

Mod Pathol

Hum Pathol

INI1-deficient tumors: diagnostic features and molecular genetics

Am J Surg Pathol

Highly aggressive behavior of malignant rhabdoid tumor: a special reference to SMARCB1/INI1 gene alterations using molecular genetic analysis including quantitative real-time PCR

J Cancer Res Clin Oncol

SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma

Am J Surg Pathol

Epithelioid sarcoma

Immunohistochemistry of soft tissue tumours—review with emphasis on 10 markers

Histopathology

ERG expression in epithelioid sarcoma: a diagnostic pitfall

Am J Surg Pathol

Differential SALL4 immunoexpression in malignant rhabdoid tumours and epithelioid sarcomas

Histopathology

Original contribution
ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: a useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor☆