Peptide screening of cerebrospinal fluid in patients with glioblastoma multiforme.

AIMS: To apply modern mass spectrometry based technology to identify possible CSF peptide markers of glioblastoma multiforme (GBM). METHODS: Mass spectrometry based peptidomics technology enables a systematic and comprehensive screening of cerebrospinal fluid (CSF) with regard to its peptide composition. Differential Peptide Display (DPD) allows the identification of single marker peptides for a target disease. Using both, we analyzed CSF samples of 11 patients harbouring a glioblastoma multiforme in comparison to 13 normal controls. RESULTS: Four CSF peptides which significantly distinguished GBM from controls in all applied statistic tests could be identified out of more than 2,000 detected CSF peptides. They were specific C-terminal fragments of alpha-1-antichymotrypsin, osteopontin, and transthyretin as well as a N-terminal residue of albumin. All molecules are constituents of normal CSF, but none has previously been reported to be significantly elevated in CSF of GBM patients. CONCLUSION: The study showed that peptidomics technology is able to identify possible biomarkers of neoplastic CNS disease. It remains to be determined if the identified elevated CSF peptides are specific for GBM. With regard to GBM, however, the more important role of CSF peptide biomarkers than aiding initial diagnosis might be early recognition of disease recurrence or monitoring of efficacy of adjuvant therapy protocols.

[Primary central nervous system lymphomas in AIDS patients]. / Linfomas primarios del sistema nervioso central en pacientes con sida.

INTRODUCTION: Primary lymphoma is the most common neoplasm of the central nervous system (CNS) in AIDS patients. METHODS: We retrospectively reviewed the clinical manifestations, neuroimaging findings, diagnostic methods used, histological characteristics, detection of Epstein-Barr virus (EBV) DNA by PCR in cerebrospinal fluid (CSF) and brain smears, and outcome of 18 HIV/AIDS patients with primary CNS lymphoma. RESULTS: The overall incidence of primary CNS lymphoma was 2.6%. Fifteen were men and mean age was 33.6 years. The most frequent clinical findings were focal neurological deficits and seizures. The mean CD4 T cell count at the time of diagnosis was 44 cells/microl. Primary CNS lymphoma presented as single, large (> 2.5 cm) lesions in 14 patients (77.8%). All the lesions were associated with a mass effect and surrounding edema. EBV DNA was detected in nine brain smears. In seven of these nine cases, EBV DNA was also found in CSF by PCR. Median survival after specific diagnosis was 75 days. CONCLUSIONS: This study upholds a link between EBV and these tumors. Primary CNS lymphoma was associated with a poor prognosis and short survival in this cohort of patients.

Elevated levels of alpha-2-Heremans-Schmid glycoprotein in CSF of patients with low-grade gliomas.

Little is known about the expression of mitogens and other tumour-related substances in the cerebrospinal fluid (CSF) of glioma patients. The aim of the current study was to determine the presence of aberrant proteins in the CSF of patients with low-grade gliomas. Lumbar puncture was performed in 8 adult patients with supratentorial low-grade gliomas at the time of diagnosis and in 7 controls. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation time of flight mass spectrometry were used to detect and quantify deviant proteins in the CSF. Two isoforms of alpha(2)-Heremans-Schmid glycoprotein (AHSG) were identified and demonstrated in higher levels in patients with low-grade gliomas compared with the control group consisting of patients with mixed neurological diagnoses (p = 0.001 and p = 0.04, respectively). In 1 patient, the level of AHSG was significantly reduced after gross total resection of the tumour. AHSG appears in the present proteome screening as a novel substance in glioma research. This glycoprotein is expressed in the fetal human brain and is believed to be involved in the embryonic development of the neocortex. Further analyses are planned to determine the significance of the increased levels of AHSG in the CSF of patients with low-grade gliomas.