Using urinary bFGF and TIMP3 levels to predict the presence of juvenile pilocytic astrocytoma and establish a distinct biomarker signature.

OBJECTIVE The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. METHODS Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age- and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. RESULTS Using optimal urinary cutoff values of bFGF > 1.0 pg/µg and TIMP3 > 3.5 pg/µg, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. CONCLUSIONS This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.

[Role of urinary basic fibroblast growth factor in differentiating hemangiomas from vascular malformation].

OBJECTIVE: To investigate a novel method to differentiate hemangioma from vascular malformation, to stage hemangiomas and to monitor the efficacy of management for hemangioma. METHODS: The urinary basic fibroblast growth factor (bFGF) concentration of 144 cases (including 69 cases of proliferating hemangiomas, 41 cases of involuting hemangiomas, 23 cases of vascular malformations and 11 negative controls) was examined using enzyme linked immunosorbent assay (ELISA). RESULTS: The differences of urinary bFGF concentration among proliferating hemangiomas, involuting hemangiomas, vascular malformations and negative control were all significant, while the differences between the latter three groups were not significant. CONCLUSIONS: Our findings suggest that examination of urinary bFGF concentration using ELISA technique is helpful in differentiating hemangioma from vascular malformation, staging hemangiomas and dynamically monitoring the efficacy of treatment for hemangiomas. Our results probably shed new light on the potential pathogenesis of hemangiomas and vascular malformation.

[Importance of bFGF ("basic fibroblast growth factor") for diagnosis and treatment of hemangiomas]. / Intérêt du dosage du bFGF ("basic Fibroblast Growth Factor") pour le diagnostic et le traitement des hémangiomes.

OBJECTIVES: Hemangiomas of infancy follow a characteristic three-phases course: proliferation, involution, regressed Proliferative endothelial cells predominate during the proliferative phase. Moreover it has been shown that patients with active angiogenesis have elevated levels of urinary bFGF (basic Fibroblast Growth Factor). PATIENTS AND METHODS: Here we report our preliminary results of urinary bFGF assay (ELISA) for the diagnosis and follow up of severe hemangioma. We also assayed bFGF in normal infants, in patients with large vascular malformations and in infants with Kasabach-Merritt syndrome. RESULTS: In the control group, urinary bFGF was elevated in new borns but nul or very low in infants. Urinary bFGF levels were normal, i.e. very low in 4 patients with a vascular malformation. In infants with a clinically proliferative hemangioma, urinary bFGF was elevated in 8 among the 10 studied. bFGF levels guided treatment in 9 patients. Urinary bFGF was elevated in 4 patients with Kasabach-Merritt syndrome. DISCUSSION: Angiogenesis is regulated by angiogenic and inhibitory factors. The angiogenic factor bFGF is an autocrine growth factor for endothelial cells and hemangioma endothelial cells expressing bFGF in their cytosol during the proliferative phase. As suggested by J. Folkman and his group, assay of urinary bFGF appears useful in differentiating between hemangioma and vascular malformation and for follow up of treated patients.