Title: Fibroblast growth factor receptor 1 (FGFR1) expression and activation in clear cell renal cell carcinoma (ccRCC).
Abstract: e15015 Background: The fibroblast growth factor (FGF) family is involved in proliferation and angiogenesis and aberrant activation of the pathway is associated with tumor neovascularization. FGF pathway activation may also provide a compensatory mechanism for angiogenesis in the setting of vascular endothelial growth factor (VEGF) blockade. However, the prognostic impact of FGF pathway activation is unknown in ccRCC. Methods: A tissue microarray representing 40 untreated ccRCC specimens was constructed with unaffected kidney parenchyma controls and analyzed by immunohistochemistry (IHC). The Ariol imaging platform was used to stratify the specimens based on intensity of staining for FGF and HIF biomarkers (FGFR1, pFRS2, HIF1 and HIF2). Progression-free survival (PFS) was defined as the number of months from chemotherapy start until death or disease progression. The relationship between marker levels and PFS was analyzed using Cox proportional hazards regression methods. All p-values were 2-tailed and considered significant at alpha < 0.05. Analyses were conducted using SAS for Windows. Results: We identified that FGFR1 expression showed a significant association with PFS using a univariate model of Cox proportional hazards regression. FGFR1 was significantly associated with PFS, with the hazard of progression greater for patients who had tumors that were FGFR1 level 3 or 4 (HR 4.56, 95% CI 1.25 to 16.66, p = 0.0218) or FGFR1 level 2 (HR 3.54, 95% CI 1.02 to 12.29, p = 0.0463) relative to the hazard among patients who had tumors with FGFR1 level 1. Conclusions: Our data indicates that the subset of ccRCC tumors with increased expression of FGFR1 is associated with a shorter PFS. These results may be used to build predictive models that identify patients that would benefit from therapeutic strategies that target both VEGF and FGF signaling.
Publication Year: 2011
Publication Date: 2011-05-20
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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