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• W2790483587 abstract "617 Background: Metabolic disruption is frequent in renal cell carcinoma (RCC). Loss of the mitochondrial fumarate hydratase (FH) enzyme is associated with enhanced glycolytic metabolism, angiogenesis and clinical aggressiveness in type 2 papillary RCC. However, FH expression has never been evaluated in clear cell RCC (ccRCC). In this study, we investigated the impact of FH expression on the outcomes of patients (pts) with metastatic ccRCC (mccRCC). Methods: We included pts with mccRCC, for whom formalin-fixed, paraffin embedded (FFPE) tissue from the primary tumor had been obtained before initiation of systemic treatment. FH levels were evaluated by immunohistochemistry (IHC), and were defined as “normal” if FH expression in most cancer cells was comparable to the adjacent normal tubular cells and “low” in the opposite case. We evaluated the association between FH levels and clinico-pathological characteristics through the chi-squared or Fisher’s exact test. The log-rank test was used to compare survival between patient subgroups. Results: We evaluated 49 mccRCC pts, of whom 36 (73.5%) had synchronous metastases. FH levels were normal in 29 (59.2%) pts and low in 20 (40.8%) pts. FH expression was not associated with patient age (p = 0.5), sex (p = 0.34), tumor grade (p = 0.66), T stage (p = 0.38), N stage (p = 0.88), metastatic disease at the time of diagnosis (p = 0.4), number of metastatic sites (p = 1) or sarcomatoid morphology (p = 0.36). 44 pts received first-line therapy with tyrosine kinase inhibitors (TKIs). In pts with low as compared to normal FH levels, median progression free survival (mPFS) during any first-line treatment was 34 and 10.1 months, respectively (HR 0.39, 95% CI 0.18-0.85; p = 0.014), while mPFS during first-line TKI therapy was 34 and 8.42 months, respectively (HR 0.4, 95% CI 0.17-0.94; p = 0.03). Median overall survival (OS) was not reached in pts with FH-low tumors, while it was 22.9 months in normally expressing ones (HR 0.14, 95% CI 0.032-0.63; p = 0.028). Conclusions: In mccRCC pts, low FH expression in primary tumors is associated with longer PFS during any first-line or TKI treatment, and also with better OS. This is the first study to reveal a prognostic and predictive role of FH levels in mccRCC." @default.
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• W2790483587 date "2018-02-20" @default.
• W2790483587 modified "2023-10-12" @default.
• W2790483587 title "Prognostic and predictive role of fumarate hydratase in metastatic clear cell renal cell carcinoma." @default.
• W2790483587 doi "https://doi.org/10.1200/jco.2018.36.6_suppl.617" @default.
• W2790483587 hasPublicationYear "2018" @default.
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