Cerebrospinal fluid (vascular endothelial growth factor) and serologic (recoverin) tumor markers for malignant glioma.
BACKGROUND
Clinically useful tumor markers have yet to be identified for malignant glioma. We report on two potential novel tumor markers, vascular endothelial growth factor (VEGF) and recoverin (protein A). VEGF is a highly specific endothelial cell activator that induces angiogenesis both in vivo and in vitro. Our study was designed to assess whether VEGF could be measured in the cerebrospinal fluid (CSF) of patients with cerebral neoplasms and used as a marker of particular tumors. We also studied serum recoverin levels in patients with various brain tumors and compared these to controls. Recoverin is a detectable serologic protein that is expressed in patients with cancer-associated retinopathy, a paraneoplastic syndrome.


METHODS
In the VEGF arm, we used a solid-phase ELISA to determine the levels of VEGF. CSF samples from patients with anaplastic astrocytoma and glioblastoma multiforme (GBM) and with metastatic and nonastrocytic brain tumors were compared with nontumor control samples. In our recoverin study, an immunoenzymetric assay was used to measure the serum recoverin levels patients with glioma and compared with controls.


RESULTS
In the VEGF arm, 89% of samples with malignant astrocytoma and 27% of nonastrocytoma samples had detectable levels of VEGF. VEGF was not detectable in normal CSF samples. The levels of VEGF were significantly higher in high-grade astrocytomas than in nonastrocytic tumors. Recoverin levels were 10-fold higher in patients with recurrent GBM relative to controls. In patients with low-grade glioma, anaplastic glioma, and GBM with no evidence of recurrence, a 3- to 5-fold increase was observed.


CONCLUSIONS
VEGF is detectable in CSF and may be a potential marker for differentiating astrocytic from nonastrocytic tumors. Recoverin is detectable in serum and may be a useful glioma tumor marker, especially for recurrent active disease. These markers may have application for tumor diagnosis, surveillance, and treatment response.
Sampath
Prakash
P
Department of Pathology, Brown Medical School, Rhode Island Hospital, Providence, RI 02903, USA. Prakash_Sampath@hotmail.com
Weaver
Charles E
CE
Sungarian
Arno
A
Cortez
Selina
S
Alderson
Lloyd
L
Stopa
Edward G
EG
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000134:cerebrospinal fluid / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051603:Recoverin / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D051603:Recoverin