Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer.

Publisher: BioMed Central Country of Publication: England NLM ID: 101319628 Publication Model: Electronic Cited Medium: Internet ISSN: 1755-8794 (Electronic) Linking ISSN: 17558794 NLM ISO Abbreviation: BMC Med Genomics Subsets: MEDLINE

Original Publication: London : BioMed Central

Leiomyomatosis*/genetics ; Leiomyomatosis*/pathology ; Leiomyomatosis*/therapy ; Fumarate Hydratase*/genetics ; Neoplastic Syndromes, Hereditary*/genetics ; Neoplastic Syndromes, Hereditary*/therapy ; Neoplastic Syndromes, Hereditary*/complications ; Neoplastic Syndromes, Hereditary*/pathology ; Uterine Neoplasms*/genetics ; Uterine Neoplasms*/pathology ; Uterine Neoplasms*/therapy ; Immunotherapy* ; Skin Neoplasms*/genetics ; Skin Neoplasms*/pathology ; Skin Neoplasms*/therapy; Humans ; Female ; Adult ; Germ-Line Mutation ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Kidney Neoplasms/therapy ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; Carcinoma, Renal Cell/therapy

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.
(© 2024. The Author(s).)

Fam Cancer. 2011 Jun;10(2):397-411. (PMID: 21404119)
Eur J Cancer. 2021 Jul;151:106-114. (PMID: 33975058)
N Engl J Med. 2016 Jan 14;374(2):135-45. (PMID: 26536169)
J Clin Oncol. 2022 Jul 20;40(21):2333-2341. (PMID: 35298296)
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3387-92. (PMID: 11248088)
J Biol Chem. 2007 Feb 16;282(7):4524-4532. (PMID: 17182618)
Int J Nephrol Renovasc Dis. 2014 Jun 20;7:253-60. (PMID: 25018647)
Eur Urol. 2016 Jul;70(1):93-105. (PMID: 26935559)
Clin Cancer Res. 2021 May 15;27(10):2910-2919. (PMID: 33658299)
Nat Genet. 2002 Apr;30(4):406-10. (PMID: 11865300)
Eur Urol. 2023 Feb;83(2):163-172. (PMID: 35715365)
Transl Androl Urol. 2020 Apr;9(2):789-793. (PMID: 32420185)
Clin Genet. 2017 Dec;92(6):606-615. (PMID: 28300276)
Fam Cancer. 2014 Dec;13(4):637-44. (PMID: 25012257)
Front Oncol. 2021 Oct 15;11:735077. (PMID: 34722283)
Fam Cancer. 2021 Jan;20(1):75-80. (PMID: 32666341)
Hum Pathol. 2022 Aug;126:136-145. (PMID: 35659509)
Eur Urol Oncol. 2020 Dec;3(6):764-772. (PMID: 31831373)
J Kidney Cancer VHL. 2020 Jul 20;7(2):6-10. (PMID: 32953419)
Int J Gynecol Pathol. 2018 May;37(3):256-261. (PMID: 28700432)
J Med Genet. 2011 Apr;48(4):226-34. (PMID: 21398687)
Clin Cancer Res. 2021 Mar 15;27(6):1734-1743. (PMID: 33414138)
J Mol Med (Berl). 2004 Aug;82(8):550-4. (PMID: 15221078)
Nat Genet. 2018 Aug;50(8):1086-1092. (PMID: 30013182)

LHGJ20210177 Henan provincial Medical Science and Technology Research Project; 222102310451 Henan provincial Scientific and technological breakthroughs

Keywords: FH gene; HLRCC-RCC; Immunotherapy; PD-L1

EC 4.2.1.2 (Fumarate Hydratase)

Hereditary leiomyomatosis and renal cell cancer

Date Created: 20240819 Date Completed: 20240819 Latest Revision: 20240927

20240927

PMC11331603

10.1186/s12920-024-01957-w

39160519