Characterization of protein S-(2-succino)-cysteine (2SC) succination as a biomarker for fumarate hydratase–deficient renal cell carcinoma

Rahul Mannan, Xiaoming Wang, Pushpinder S. Bawa, Seema Chugh, Anya K. Chinnaiyan, Roshni Rangaswamy, Yuping Zhang, Xuhong Cao, Steven C. Smith, Kiril Trpkov, Sean R. Williamson, Ankur R. Sangoi, Sambit Mohanty, Jesse K. McKenney, Sounak Gupta, Cristina Magi-Galluzzi, Pedram Argani, Adeboye O. Osunkoya, Arul M. Chinnaiyan, Saravana M. DhanasekaranRohit Mehra

Research output: Contribution to journalArticlepeer-review

Abstract

Fumarate hydratase (FH)–deficient renal cell carcinoma (RCC) is an aggressive, rare genetic disease affecting the kidney and other organ systems. We constructed a specialized multi-institutional cohort of 20 primary FH-deficient RCC cases with aims of characterizing a new commercially available antibody, S-(2-succino)-cysteine (2SC). Herein, we present our findings on the biomarker characterization and performance of 2SC expression by immunohistochemistry (IHC) in FH-deficient RCC and other common and rare RCC subtypes. Morphological assessment revealed characteristic cytomorphologic features and a majority (55%) of FH-deficient RCC had mixed architectural growth patterns. We observed predominantly diffuse and strong cytoplasmic staining with limited nuclear positivity for 2SC staining on IHC. Receiver operating characteristic curves (ROC) for 2SC identified the threshold IHC score (cutoff) as 90, with the sensitivity and specificity being 100% and 91%, respectively. The findings of the present study along with the prior evidence in literature encourage utilization of 2SC as a positive marker along with the loss of FH expression by anti-FH IHC staining as a negative marker, in clinical and/or pathologic scenarios when considering FH-deficient RCC in the differential diagnosis. FH/2SC+ may serve as a comprehensive IHC panel in identifying such cases and excluding morphologically similar entities.

Original languageEnglish (US)
Pages (from-to)102-113
Number of pages12
JournalHuman pathology
Volume134
DOIs
StatePublished - Apr 2023

Keywords

  • 2SC
  • Biomarker
  • FH
  • HLRCC
  • Renal cell carcinoma
  • Succination

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Characterization of protein S-(2-succino)-cysteine (2SC) succination as a biomarker for fumarate hydratase–deficient renal cell carcinoma'. Together they form a unique fingerprint.

Cite this