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.

[Detection and clinical significance of urinary epidermal growth factor in brain tumor patients].

OBJECTIVE: To investigate the clinical significance of urinary epidermal growth factor (EGF) in patients with brain tumors. METHODS: The levels of EGF in urine samples collected from 20 patients (9 low grade astrocytomas, 6 anaplastic astrocytomas, and 5 meningiomas) and 5 healthy individuals were determined. EGF levels were measured by radioimmunoassay technique. A preoperative and one postoperative determination were performed. RESULTS: Preoperative urinary EGF levels of astrocytoma patients were statistically higher than those of meningioma patients and the controls (P < 0.01). Preoperative urinary EGF levels showed a positive correlation with the degree of malignance in the astrocytoma patients (P < 0.05). A significant decrease of the postoperative levels of EGF was observed in the astrocytoma patients who underwent gross total resection (P < 0.01). The pre/postoperative urinary EGF levels of the meningioma patients showed no significant fluctuations and showed no significant difference with those of healthy individuals (P > 0.05). CONCLUSION: The urinary EGF levels of astrocytoma patients correlate with the WHO grade of malignance and significantly decrease after gross total removal. Urinary EGF may be of practical value in diagnosing and evaluating the surgical efficacy of astrocytomas.

PCR detection of JC virus DNA in the brain tissue of a 9-year-old child with pleomorphic xanthoastrocytoma.

Pleomorphic xanthoastrocytoma (PXA) is a rare cerebral tumor of young adults with a slow growth and a good prognosis. Due to its peculiar histopathological findings, the tumor resemble to the lytic phase of progressive multifocal leukoencephalopathy (PML), a JC Virus (JCV) induced disease. For these reasons, the presence of JCV genoma and viral particles were searched for by means of nested polymerase chain reaction (nPCR) and electron microscopy (EM) in a 9-year-old child with PXA. Although EM did not reveal any viral particles, nPCR did reveal genomic sequences of the LT, R, and VP1 regions of JCV. Sequence analysis showed that the R region was mutated with respect to the archetypal form thus yielding the Mad 4 variant of JCV previously reported as being oncogenic in animals. We suggest that JCV may have played a role in the development of this tumor.