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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
Author(s) -
Clarke Blaise A,
Witkowski Leora,
Ton Nu Tuyet N,
Shaw Patricia A,
Gilks C Blake,
Huntsman David,
Karnezis Anthony N,
Sebire Neil,
Lamovec Janez,
Roth Lawrence M,
Stewart Colin J R,
Hasselblatt Martin,
Foulkes William D,
McCluggage W Glenn
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12988
Subject(s) - smarca4 , biology , immunohistochemistry , pathology , staining , small cell carcinoma , ovary , carcinoma , gene expression , medicine , genetics , chromatin remodeling , immunology , gene
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 .