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
- 1 Department of Urology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- 2 The Graduate School of Fujian Medical University, Fuzhou 350000, Fujian, P.R. China
- 3 Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- 4 Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
- 5 Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian, P.R. China
Received: October 3, 2023 Accepted: December 27, 2023 Published: February 19, 2024
https://doi.org/10.18632/aging.205549How to Cite
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.
Abbreviations
RCC: renal cell carcinoma; FH-dRCC: fumarate hydratase-deficient renal cell carcinoma; HLRCC: with hereditary leiomyomatosis and renal cell carcinoma; CL: cutaneous leiomyomas; MUL: multiple uterine leiomyomas; WHO: World Health Organization; IHC: immunohistochemical; NCCN: National Comprehensive Cancer Network; RN: radical nephrectomy; T2 pRCC: type 2 papillary renal cell carcinoma; PN: partial nephrectomy; CDC: collecting duct carcinoma; ISUP: International Society of Urological Pathology; 2-SC: 2-succino-cysteine; ORR: objective response rate; LN: lymph node; AWOD: alive without disease; AWD: alive with disease; DOD: die of disease; DOAD: die of another disease; NA: not available; ICI: immune checkpoint inhibitor; MKI: multi-kinase inhibitor; CT: chemotherapy; CSS: cancer-specific survival; SE: secondary endpoint; DFS: disease-free survival; ORR: objective response rate; DCR: disease control rate.