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

Autor:	Anthony N. Karnezis, W. Glenn McCluggage, Janez Lamovec, Neil J. Sebire, Tuyet Nhung Ton Nu, C. Blake Gilks, Patricia Shaw, Leora Witkowski, David G. Huntsman, Martin Hasselblatt, Blaise A. Clarke, William D. Foulkes, Colin J.R. Stewart, Lawrence M. Roth
Rok vydání:	2016
Předmět:	0301 basic medicine Pathology medicine.medical_specialty Histology Ovary Carcinoma Ovarian Epithelial Biology Sensitivity and Specificity Small-cell carcinoma Pathology and Forensic Medicine Diagnosis Differential 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor medicine Carcinoma Humans Neoplasms Glandular and Epithelial Carcinoma Small Cell SMARCB1 Nuclear protein Ovarian Neoplasms DNA Helicases Nuclear Proteins General Medicine medicine.disease Immunohistochemistry Staining 030104 developmental biology medicine.anatomical_structure Tissue Array Analysis 030220 oncology & carcinogenesis SMARCA4 Cancer research Female Transcription Factors
Zdroj:	Histopathology. 69:727-738
ISSN:	0309-0167
DOI:	10.1111/his.12988
Popis:	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 SMARCA4 (BRG1), 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 SMARCA4/BRG1 protein. Furthermore, three cases of SCCOHT with retained SMARCA4 protein expression showed loss of SMARCB1/INI1 expression. The aim of this study was to assess the sensitivity and specificity of loss of SMARCA4 expression as a diagnostic test for SCCOHT. Methods and results We performed SMARCA4 and SMARCB1 staining in 245 tumours, many of which were potentially in the differential diagnosis of SCCOHT. We also stained 56 cases of SCCOHT for SMARCA4 and 37 of these for SMARCB1. Fifty-four of the SCCOHT cases showed complete absence of SMARCA4 expression. The two cases with retained expression showed molecular alteration of SMARCA4. Of the 217 other neoplasms with interpretable staining, all retained SMARCA4 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 SMARCB1 expression. Loss of SMARCA4 expression had a sensitivity of 96.55% and specificity of 100%. Conclusions Loss of SMARCA4 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.
Databáze:	OpenAIRE
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