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Updated: Sep 13, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Clinical, Pathologic, and Genetic Correlates of Nuclear Grade in von Hippel-Lindau-associated Renal Cell Carcinoma
Lauren Loebach1, Braden Millan1, Maria Antony1
1Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Objective:
To evaluate the proportion of von Hippel-Lindau (VHL) patients with high-grade disease and analyze the association of clinical, pathologic, and genetic factors with high-grade disease.
Methods:
Clear cell renal cell carcinoma (ccRCC) specimens resected from VHL patients between 2006 and 2021 at the National Cancer Institute were evaluated. Pathologic, demographic, and genetic data were obtained from clinical records. Multivariate logistic regression models analyzed the association between pathologic grade and demographic information, tumor size, history of previous ipsilateral partial nephrectomy (PN), and germline VHL gene variant.
Results:
From 229 patients with VHL, we identified 2555 ccRCC tumor specimens, of which 203 (7.94%) tumors were high-grade. Over the whole study period, 99 (43.2%) patients developed a high-grade tumor. Older age (odds ratio (OR) 1.02, P<.0001) and increasing tumor size (OR 1.58, P<.0001) were associated with high-grade pathology. Prior ipsilateral PN (OR 2.10, P=.002) and germline frameshift VHL variants (OR 2.38, P=.01) were also associated with high-grade pathology.
Conclusion:
These results demonstrate a strong association between tumor size, age at surgery, re-operative surgery status, and VHL frameshift genetic variant and high-grade pathology in VHL-associated RCC. These factors can be used clinically to assist in surgical intervention decision-making.
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