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

• Published in: Aging (Albany, NY.) Vol. 16; no. 4; pp. 3631 - 3646
• Main Authors: Bai, Junjie, Li, Xiaoyan, Wen, Yahui, Lu, Qing, Chen, Ru, Liu, Rong, Shangguan, Tong, Ye, Yushi, Lin, Jun, Cai, Weizhong, Kang, Deyong, Chen, Jianhui
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 19.02.2024
• Subjects: Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Female; Fumarate Hydratase - genetics; Fumarate Hydratase - metabolism; Humans; Kidney Neoplasms - diagnosis; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Leiomyomatosis - diagnosis; Leiomyomatosis - genetics; Leiomyomatosis - pathology; Research Paper; Retrospective Studies; Skin Neoplasms - genetics; Treatment Outcome; Uterine Neoplasms - genetics; Uterine Neoplasms - pathology; Vascular Endothelial Growth Factor A; renal cell carcinoma; molecular; papillary; hereditary leiomyomatosis and renal cell carcinoma; immunohistochemistry; fumarate hydratase
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.205549

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). 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. 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 ( = 0.042) and DFS ( < 0.001). The genomic sequencing revealed 9 novel mutations. 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.