Loss of SMARCA4 (BRG1) protein expression as determined by immunohistochemistry in small‐cell carcinoma of the ovary, hypercalcaemic type distinguishes these tumours from their mimics

Aims Molecular investigation of small‐cell carcinoma of the ovary, hypercalcaemic type ( SCCOHT ) has revealed that it is a monogenetic tumour characterized by alteration of SMARCA 4 ( BRG 1 ), encoding a member of the switch/sucrose non‐fermentable ( SWI / SNF ) chromatin remodelling complex. A large majority of cases show loss of expression of the corresponding SMARCA 4/ BRG 1 protein. Furthermore, three cases of SCCOHT with retained SMARCA 4 protein expression showed loss of SMARCB 1/ INI 1 expression. The aim of this study was to assess the sensitivity and specificity of loss of SMARCA 4 expression as a diagnostic test for SCCOHT . Methods and results We performed SMARCA 4 and SMARCB 1 staining in 245 tumours, many of which were potentially in the differential diagnosis of SCCOHT . We also stained 56 cases of SCCOHT for SMARCA 4 and 37 of these for SMARCB 1. Fifty‐four of the SCCOHT cases showed complete absence of SMARCA 4 expression. The two cases with retained expression showed molecular alteration of SMARCA 4 . Of the 217 other neoplasms with interpretable staining, all retained SMARCA 4 expression. Although the majority showed diffuse, strong nuclear expression, a heterogeneous, typically weak staining pattern was present in 13% of cases. All 37 cases of SCCOHT tested and all other neoplasms, apart from three malignant rhabdoid tumours, showed retained nuclear SMARCB 1 expression. Loss of SMARCA 4 expression had a sensitivity of 96.55% and specificity of 100%. Conclusions Loss of SMARCA 4 expression is sensitive and specific for SCCOHT . Although some mimics show heterogeneous expression, there is retention of nuclear staining in at least a part of the tumour; therefore, only complete loss of staining should be regarded as being supportive of SCCOHT .