SWI/SNF protein expression status in fumarate hydratase-deficient renal cell carcinoma: immunohistochemical analysis of 32 tumors from 28 patients. Hum Pathol 2018 Jul;77:139-146
Date
04/25/2018Pubmed ID
29689242DOI
10.1016/j.humpath.2018.04.004Scopus ID
2-s2.0-85047638969 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive RCC type, originally described in the setting of hereditary leiomyomatosis and RCC syndrome, which is defined by germline FH gene inactivation. Inactivation of components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex is involved in renal medullary carcinoma (SMARCB1/INI1 loss), clear cell RCC (PBRM1 loss), and subsets of dedifferentiated RCC of clear cell, chromophobe, and papillary types (loss of different SWI/SNF components). FH-RCC and SWI/SNF-deficient RCC share anaplastic nuclear features and highly aggressive course. We analyzed 32 FH-RCCs from 28 patients using 7 commercially available SWI/SNF antibodies (SMARCB1/INI1, SMARCA2, SMARCA4, SMARCC1, SMARCC2, PBRM1, and ARID1A). Variable loss of SMARCB1, ARID1A, and SMARCC1 was observed in 1 of 31, 2 of 31, and 1 of 29 evaluable cases, respectively; 3 of these 4 SWI/SNF-deficient tumors had confirmed FH mutations. No correlation of SWI/SNF loss with solid or sarcomatoid features was observed. Two tumors with SMARCB1 and ARID1A deficiency had available SWI/SNF molecular data; both lacked SMARCB1 and ARID1A mutations. The remaining 5 SWI/SNF components were intact in all cases. Especially PBRM1 seems not to be involved in the pathogenesis or progression of FH-RCC. Our data showed that a subset of FH-RCC (12%) have a variable loss of SWI/SNF complex subunits, likely as secondary genetic events. This should not be confused with SWI/SNF-deficient RCC of other types. Evaluation of FH and SWI/SNF together with comprehensive molecular genetic profiling is needed to explore possible prognostic implications of FH/SWI-SNF double deficiency and to better understand the somatic mutation landscape in high-grade RCC.
Author List
Agaimy A, Amin MB, Gill AJ, Popp B, Reis A, Berney DM, Magi-Galluzzi C, Sibony M, Smith SC, Suster S, Trpkov K, Hes O, Hartmann AMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Carcinoma, Renal Cell
Chromosomal Proteins, Non-Histone
DNA Helicases
DNA-Binding Proteins
Female
Fumarate Hydratase
Humans
Immunohistochemistry
Kidney Neoplasms
Male
Middle Aged
Mutation
Nuclear Proteins
Transcription Factors
Young Adult
