#0765

Genotypic characterization and diagnostic efficacy of aldo-keto reductase family 1 member B10 (AKR1B10) immunohistochemistry in fumarate hydratase-deficient renal cell carcinoma among Taiwanese patients

Y. Lin¹, T. Lin^2,3, Y. Peng^4,5, E. Huang^6,7, W. Huang^6,8,7, Y. Chang^6,9, H. Chung^6,3, T. Wei^6,9, C. Tsai⁶

¹Tapei Veterans General Hospital, Department of Medical Education, Taipei, Taiwan
²Tapei Veterans General Hospital, Department of Urology, Taipei, Taiwan
³College of Medicine and Shu-Tien Urological Research Center, National Yang Ming Chiao Tung University, Department of Urology, Taipei, Taiwan
⁴Tapei Veterans General Hospital, Department of Pathology and Laboratory Medicine, Taipei, Taiwan
⁵National Defense Medical Center, Department of Pathology and Parasitology, Taipei, Taiwan
⁶Taipei Veterans General Hospital, Department of Urology, Taipei, Taiwan
⁷College of Medicine and Shu-Tien Urological Science Research Center, National Yang Ming Chiao Tung University, Department of Urology, Taipei, Taiwan
⁸National Yang Ming Chiao Tung University, Department of Physiology, School of Medicine, Taipei, Taiwan
⁹Shu-Tien Urological Institute, National Yang-Ming University, Department of Urology, School of Medicine, Taipei, Taiwan

Introduction:

The utility of immunohistochemistry (IHC) for fumarate hydratase (FH) and S-(2-succino)-cysteine (2SC) has been investigated to differentiate FHDRCC. Recently, IHC for aldo-keto reductase family 1 member B10 (AKR1B10) was reported as a novel and precise diagnostic marker for FHDRCC. This study aims to confirm the diagnostic efficacy of AKR1B10 IHC in FHDRCC and to characterize the genotypic and phenotypic features of FHDRCC in Taiwanese patients.

Material and methods:

We analyzed 9 tumor samples diagnosed with FHDRCC by surgical pathology, as well as by FH and 2SC IHC. AKR1B10 IHC was applied to the tumor samples and their adjacent normal renal parenchyma . Furthermore, we used whole-exome sequencing to investigate genetic variants in the FH gene and other co-occurring oncogenic alterations in 9 patients, including 7 who underwent tumor–normal paired analysis and 2 who underwent tumor-only analysis.

Results:

Among the tumor samples, 6 showed diffuse positivity, 2 showed focal positivity, and 1 was negative. Among the normal renal parenchyma samples, 8 were negative and 1 showed focal positivity. From the genomic analyses, we found that all 9 patients carried FH gene mutations. Among the 7 patients who underwent tumor-normal paired analysis, all had germline FH mutations and 1 also had somatic FH mutation. For the remaining 2 patients, it was not possible to determine whether their FH mutations were germline or somatic. Additional oncogenic alterations in genes were also identified.