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Distinctive clinicopathological features of Von Hippel-Lindau-associated hereditary renal cell carcinoma: A single-institution study.

ABSTRACT: Von Hippel-Lindau (VHL) disease is a genetic syndrome that involves the development of tumors in numerous organs. The kidney is one of the most frequently affected organs, and patients with VHL and renal tumors require repeated nephrectomy. The present study aimed to further determine the clinicopathological characteristics of patients with VHL-associated renal cell carcinoma (RCC), which may allow more rational clinical treatment decisions. This study included 27 patients with VHL who underwent radical or partial nephrectomy at the Peking University First Hospital between January 2010 and April 2018. The clinicopathological characteristics and prognosis of the patients were retrospectively reviewed. The expression of RCC-associated molecular markers was evaluated by immunohistochemistry. The mean size of the renal tumors was 4.3±2.0 cm (range 1.3-9.5 cm). The pathological type in 26 cases (96.3%) was clear cell RCC (CCRCC), whereas only one patient was diagnosed with CCRCC and clear cell papillary RCC. Renal cysts with a clear cell lining were observed, and RCC cell clusters were scattered in renal cyst cavities. Among the 27 patients, 21 (77.8%) were diagnosed with stage IA/T1N0M0, according to Tumor-Node-Metastasis staging, and 16 (59.3%) had grade 1 tumors. The mean postoperative follow-up duration was 39.0±24.0 months (range, 1.7-96.5 months). No metastasis or VHL-associated mortality was observed. VHL-associated RCC is a relatively low-risk disease, and a tumor size of 4 cm was determined as a threshold for nephron-sparing surgery. In addition, to prevent tumor cell dispersion, renal cysts should be carefully treated. A comprehensive understanding of the clinicopathological characteristics and underlying mechanisms of RCC associated with VHL syndrome may improve patient prognosis.

SUBMITTER: Hong B

PROVIDER: S-EPMC6444392 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Distinctive clinicopathological features of Von Hippel-Lindau-associated hereditary renal cell carcinoma: A single-institution study.

Hong Baoan B Zhang Zhongyuan Z Zhou Jingcheng J Ma Kaifang K Zhang Jiufeng J Cai Lin L Zhang Ning N Gong Kan K

Oncology letters 20190301 5

Von Hippel-Lindau (VHL) disease is a genetic syndrome that involves the development of tumors in numerous organs. The kidney is one of the most frequently affected organs, and patients with VHL and renal tumors require repeated nephrectomy. The present study aimed to further determine the clinicopathological characteristics of patients with VHL-associated renal cell carcinoma (RCC), which may allow more rational clinical treatment decisions. This study included 27 patients with VHL who underwent ...[more]

PMID: 30944649

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Project description:BACKGROUND:Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function. METHODS:VHL mutational status was determined by direct DNA sequencing on tumor tissue. NK cytotoxicity was measured against specific target cells K562, VHL-wild type (CAKI-1) and VHL-mutated (A498) human renal cancer cells through externalization of CD107a and IFN-? production. Activating NK receptors, NKp30, NKp44, NKp46, NKG2D, DNAM-1, NCAM-1 and Fc?RIIIa were evaluated through quantitative RT-PCR. RCC tumoral Tregs were characterized as CD4+CD25+CD127lowFoxp3+ and Treg function was evaluated as inhibition of T-effector proliferation. RESULTS:VHL mutations were detected in 26/55 (47%) RCC patients. IL-2 activated whole-blood samples (28 VHL-WT-RCC and 23 VHL-MUT-RCC) were evaluated for NK cytotoxicity toward human renal cancer cells A498, VHL-MUT and CAKI-1, VHL-WT. Efficient NK degranulation and increase in IFN-? production was detected when IL-2 activated whole-blood from VHL-MUT-RCC patients were tested toward A498 as compared to CAKI-1 cells (CD107a+NK: 7?±?2% vs 1?±?0.41%, p?=?0.015; IFN-?+NK: 6.26?±?3.4% vs 1.78?±?0.9% respectively). In addition, IL-2 activated NKs induced higher CD107a exposure in the presence of RCC autologous tumor cells or A498 as compared to SN12C (average CD107a+NK: 4.7 and 2.7% vs 0.3% respectively at 10E:1?T ratio). VHL-MUT-RCC tumors were NKp46+ cells infiltrated and expressed high NKp30 and NKp46 receptors as compared to VHL-WT-RCC tumors. A significant lower number of Tregs was detected in the tumor microenvironment of 13 VHL-MUT-RCC as compared to 13 VHL-WT-RCC tumors (1.84?±?0.36% vs 3.79?±?0.74% respectively, p?=?0.04). Tregs isolated from VHL-MUT-RCC patients were less suppressive of patients T effector proliferation compared to Tregs from VHL-WT-RCC patients (Teff proliferation: 6.7?±?3.9% vs 2.8?±?1.1%). CONCLUSIONS:VHL tumoral mutations improve NKs effectiveness in RCC patients and need to be considered in the evaluation of immune response. Moreover therapeutic strategies designed to target NK cells could be beneficial in VHL-mutated-RCCs alone or in association with immune checkpoints inhibitors.

Dataset Information

Distinctive clinicopathological features of Von Hippel-Lindau-associated hereditary renal cell carcinoma: A single-institution study.

Publications

Distinctive clinicopathological features of Von Hippel-Lindau-associated hereditary renal cell carcinoma: A single-institution study.

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