2SC/S-(2-succino)cysteine Polyclonal

Succination is a stable post-translational modification of cysteine residues, which modifies protein function or turnover in response to a changing intracellular redox environment. Succination occurs when the Krebs cycle intermediate, fumarate, reacts with cysteine yielding S-(2-succino)cysteine (2SC). 2SC therefore serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes, and cancer. Fumarate hydratase (FH)-deficient renal cell carcinoma is an aggressive neoplasm driven by inactivating mutations of the FH gene, which cause metabolites like 2SC to accumulate and trigger cascades supporting malignant transformation. Combining FH loss and positive 2SC staining is a diagnostic approach, particularly in the context of FH-deficient renal cell carcinoma (FHdRCC) and Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC). FHdRCC, a rare and aggressive subtype of RCC, is characterized by a functional loss of the FH gene, which leads to the accumulation of fumarate, which reacts with cysteine to form 2SC, a byproduct that can be detected with immunohistochemistry (IHC). FHdRCC and HLRCC, a genetic predisposition to FHdRCC and other related tumors, can be identified by IHC with anti-FH antibodies, which will be negative in FH-deficient cells, and anti-2SC antibodies, which will be positive in FH-deficient cells.