Elsevier

Human Pathology

Volume 40, Issue 3, March 2009, Pages 349-355
Human Pathology

Original contribution
Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

https://doi.org/10.1016/j.humpath.2008.08.007Get rights and content

Summary

Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of epithelioid sarcoma. In addition, the histopathologic differences between proximal-type epithelioid sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 epithelioid sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type epithelioid sarcoma and 27 (93.1%) distal-type epithelioid sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type epithelioid sarcoma. Epithelioid sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type epithelioid sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type epithelioid sarcoma (P = .001). Therefore, proximal-type epithelioid sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type epithelioid sarcoma from malignant rhabdoid tumor.

Introduction

The SMARCB1/INI1 gene is a member of the adenosine triphosphate–dependent SWI/SNF chromatin-remodeling complex, suggesting that it is a candidate tumor suppressor gene in malignant rhabdoid tumor (MRT) [1], [2], [3], [4], [5], [6], [7]. The SMARCB1/INI1 gene functions as an indirect suppressor of the cell cycle or mutually increases retroviral DNA intake with some viral proteins [2], [4], [7], [8]. Theoretically, therefore, it could be involved in other malignancies.

In previous studies of MRT cases, there was no detectable expression of the SMARCB1/INI1 protein in tumor cells with the SMARCB1/INI1 antibody, whereas all the other kinds of tumor cells showed SMARCB1/INI1 protein expression [9], [10], [11], [12], [13], [14]. Therefore, immunohistochemical testing for the SMARCB1/INI1 antibody has been considered useful in confirming the histologic diagnosis of MRT [9], [10], [11], [12], [13], [14]. However, Modena et al [15] recently reported the presence of SMARCB1/INI1 gene alterations and the absence of the SMARCB1/INI1 protein in several cases of epithelioid sarcoma (ES), including cases of both proximal-type and distal-type ES. Some data exist regarding the histologic and immunohistochemical differences between ES, especially proximal-type ES, and MRT, but such findings are not yet conclusive [3], [13], [16].

In the present study, we analyzed the frequency of SMARCB1/INI1 protein expression in a large series of ES cases, with special emphasis on the frequency in proximal-type ES. In addition, we searched for alterations in the SMARCB1/INI1 gene, such as homozygous deletions and mutations, in several of the patients with ES.

Section snippets

Patients and DNA extraction

Fifth-four formalin-fixed, paraffin-embedded ES specimens (proximal-type ES, 25 cases; distal-type ES, 29 cases), registered at the Department of Anatomic Pathology between 1980 and 2007, were available. In all the cases, the diagnosis was based on light microscopic examination with hematoxylin-eosin staining according to the most recent World Health Organization classification [17]. Moreover, immunoperoxidase procedures using the streptavidin-biotin peroxidase method were carried out when

Clinical and histologic findings

The clinicopathologic findings of the 54 cases of ES are summarized in Table 1. Histologically, distal-type ES typically shows a nodular or multinodular proliferation of mainly spindle-shaped cells admixed with epithelioid cells (conventional type). In contrast, proximal-type ES typically reveals a diffuse proliferation of large epithelioid carcinoma–like cells with marked cytologic atypia and fragmental occurrence of rhabdoid features.

SMARCB1/INI1 Immunoreactivity

The results of the immunohistochemical analysis are

Discussion

ES is a rare soft tissue sarcoma that occurs in the proximal region of the extremities and trunk (proximal-type ES) and the distal extremities (distal-type ES). Histologically, rhabdoid features are frequently observed, especially in proximal-type ES [3], [17]. Therefore, the clinicopathologic differences between ES and MRT, especially when comparing proximal-type ES with MRT, are still controversial [13].

Several factors distinguishing ES from MRT have been reported. Clinically, the peak age

Acknowledgment

The English used in this manuscript was revised by KN International (http://www.kninter.com/).

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    This study was supported by a Grant-in-Aid for Scientific Research (C) (no. 18590332) from the Japan Society for the Promotion of Science, Tokyo, Japan.

    1

    K Kohashi and T Izumi contributed equally to this work.

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