Concurrent loss of INI1, PBRM1, and BRM expression in epithelioid sarcoma: implications for the cocontributions of multiple SWI/SNF complex members to pathogenesis.

Abstract

The loss of INI1 (SMARCB1) expression, caused by SMARCB1 (INI1, SNF5L4, BAF47) inactivation, frequently occurs in epithelioid sarcoma (ES) and could aid in confirming the diagnosis. Except for INI1, the expression of switch in mating type/sucrose nonfermentation complex members in ES has never been examined. In this study, the expression of key subunits of this complex-INI1, BRG1 (SMARCA4), BRM (SNF2L2, SMARCA2), PBRM1 (hPB1, BAF180), and BAF155 (SMARCC1)-was analyzed in 23 ES cases: 15 conventional and 8 proximal type. All of the cases were reviewed and reclassified by hematoxylin-eosin staining and immunostaining for cytokeratin AE1/3, epithelial membrane antigen, CD34, vimentin, and INI1 expression. Of the 23 ES cases, 19 (82.6%) showed a loss of PBRM1, and 18 (78.3%), a loss of INI1. In most cases (17, 73.9%), loss of INI1 and PBRM1 expression was observed. The pattern of PBRM1 expression was similar to that of INI1, that is, not correlated with changes in cellular morphology. The concurrent loss of BRM, PBRM1, and INI1expression was detected in 2 cases with pure rhabdoid tumor features. The frequent observation of concurrent loss of INI1 and PBRM1 suggests that certain switch in mating type/sucrose nonfermentation complex components might act synergistically in the pathogenesis of ES by unknown mechanisms and that these components could provide new targets for therapy. The usefulness of PBRM1 as a biomarker of ES and its mechanism in ES require further investigation. Loss of BRM in ES with pure rhabdoid features suggests that BRM might be involved in the underlying mechanisms of this type of ES.