Validating a 2SC immunohistochemistry protocol for the diagnosis of fumarate hydratase-deficient tumours at LabPLUS

Introduction: Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is an aggressive tumour characterised by biallelic inactivation of the FH gene. The tumour may arise from somatic mutations or germline variants. The latter may be associated with hereditary leiomyomatosis and renal cell carcinoma syndrome, which predisposes individuals to developing both RCC and leiomyomata. 1 Loss of FH expression by immunohistochemistry (IHC) is commonly used to facilitate the diagnosis; however, while highly specific, it is less sensitive. Sensitivity can be improved through concurrent use of S-(2-succino)-cysteine (2SC) IHC. 2 This study aims to validate 2SC IHC in our laboratory prior to its implementation in the diagnostic IHC panel for FH-deficient RCC and leiomyomata.