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Research Paper|Volume 16, Issue 4|pp 3631—3646

The clinicopathologic and molecular features, and treatment outcome of fumarate hydratase-deficient renal cell carcinoma: a retrospective comparison with type 2 papillary renal cell carcinoma

Junjie Bai1,2, Xiaoyan Li3, Yahui Wen2,4,5, Qing Lu1, Ru Chen1, Rong Liu1, Tong Shangguan1,2, Yushi Ye1,2, Jun Lin1,2, Weizhong Cai1, Deyong Kang3, Jianhui Chen1
  • 1Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
  • 2The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
  • 3Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
  • 4Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
  • 5Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
* Equal contribution
Received: October 3, 2023Accepted: December 27, 2023Published: February 19, 2024
https://doi.org/10.18632/aging.205549

Copyright: © 2024 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: To compare clinicopathologic, molecular features, and treatment outcome between fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and type 2 papillary renal cell carcinoma (T2 pRCC).

Methods: Data of T2 pRCC patients and FH-dRCC patients with additional next-generation sequencing information were retrospectively analyzed. The cancer-specific survival (CSS) and disease-free survival (DFS) were primary endpoint.

Results: A combination of FH and 2-succino-cysteine (2-SC) increased the rate of negative predictive value of FH-dRCC. Compared with T2 pRCC cases, FH-dRCC cases displayed a greater prevalence in young patients, a higher frequency of radical nephrectomy. Seven FH-dRCC and two T2 pRCC cases received systemic therapy. The VEGF treatment was prescribed most frequently, with an objective response rate (ORR) of 22.2% and a disease control rate (DCR) of 30%. A combined therapy with VEGF and checkpoint inhibitor reported an ORR of 40% and a DCR of 100%. FH-dRCC cases showed a shortened CSS (P = 0.042) and DFS (P < 0.001). The genomic sequencing revealed 9 novel mutations.

Conclusions: Coupled with genetic detection, immunohistochemical biomarkers (FH and 2-SC) can distinguish the aggressive FH-dRCC from T2 pRCC. Future research is awaited to illuminate the association between the novel mutations and the clinical phenotypes of FH-dRCC in the disease progression.