Biomarkers for Prognosis of Glioblastoma (GBM)

Matrix metalloproteinases (MMP) -2 and -9 belong to a multigene family of degradative enzymes
implicated in the neoangiogenesis required for tumor growth. In the central nervous system
(CNS), MMP-2, MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL) are overexpressed
in orthotopic models and also in human brain tumor specimens. Furthermore, serum and urinary
levels of these markers have been shown to correlate with the presence and status of brain
tumors in all types of primary brain tumors. A major challenge in the treatment of primary
brain tumors is the dependence on magnetic resonance imaging (MRI) to differentiate disease
progression from treatment-related change. This is particularly challenging in glioblastomas
(GBM) where multimodality therapy with radiation and chemotherapy is commonly used and can
lead to pseudoprogression and treatment-related tissue necrosis, both of which can masquerade
as true tumor progression. Often we are faced with the decision to treat based on imaging
findings alone or to recommend that patients have another invasive surgery. We hypothesize
that MMP-2, MMP-9 and NGAL will: 1) be detected on tumor tissue by immunohistochemistry and
not on non-tumor (epilepsy) brain tissue, 2) parallel the course of disease in the urine
and/or serum of patients and 3) remain unchanged in the event of pseudoprogression and
treatment related imaging changes. Quality of life, patient symptoms, and cognitive function
are vitally important in patients with GBM. Quality of life and selected symptoms will also
be assessed and correlated with serum and urine biomarkers. We hope to confirm the utility of
MMP-2, MMP-9 and NGAL in the management of GBM.

Inclusion Criteria:

1. Subjects scheduled for a surgical excision or biopsy as ordered by his/her clinic or
inpatient physician for epilepsy OR subjects newly diagnosed with high grade (grade
IV) glioma (The performance of this procedure will be under standard of care surgical
guidelines.)

- non-tumor tissue controls from subjects undergoing surgery for epilepsy

- tumor tissue from subjects undergoing surgery for grade IV glioma

2. Epilepsy subject identified as a control undergoing surgery must willingly provide
pre-op and post-op serum and urine samples for research

3. GMB subject must willingly provide blood and urine samples pre-op and post-op as well
as blood and urine samples for research and QOL measurements taken at protocol
specific time points

4. GBM subject plans to receive clinical care visits which coincide with MRIs and/or with
a change in symptoms and any secondary surgical resections and/or biopsies solely at
UNMC/TNMC

5. Subjects must willingly give signed informed consent

6. Age 19 years or older (the age of consent in Nebraska)

7. Women must not be pregnant due to teratogenic effects of MRI

Exclusion Criteria:

1. Inability to fulfill the requirements of the protocol

2. No serious disease or condition that, in the opinion of the investigator, would
compromise the patient's ability to participate in the study

3. Known to be positive for HIV or infectious hepatitis, type A, B or C or active
Hepatitis

4. Subjects newly diagnosed with high grade (grade IV) glioma (GBM) unable to be followed
by MRI due to

- Pacemaker

- Chronic kidney disease stage 3-5 (Glomerular Filtration Rate <60)

- Unable to lay flat for 90 minutes

- Any metallic foreign body not approved for MRI

- Known hypersensitivity to Gadolinium contrast or other required for MRI