Original contributionInfrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing 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.
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K Kohashi and T Izumi contributed equally to this work.