Key Biomarkers
Biomarkers are biological molecules that show up in blood, body fluids, or tissues, such as tumors. These molecules could include genes, proteins, or tumor markers — leftovers from cancer cell activity.
“Molecular markers play a significant role in helping doctors choose the best treatment tailored specifically to the cancer type,” Santos says. “They also allow us to predict how the tumor will behave after being exposed to treatments.”
Your glioblastoma pathology report may include a number of common biomarkers.
IDH Mutation Status
IDH genes play a big role in cell function, and almost all glioblastomas are “IDH wild-type,” which means they aren’t mutated.
Tumors with an IDH mutation grow slowly, but most glioblastomas don’t have this mutation, which makes them more aggressive, says Nitesh V. Patel, MD, a brain and tumor neurosurgeon and the codirector of the neurosurgical oncology program at Hackensack Meridian Jersey Shore University Medical Center in Neptune, New Jersey.
“This [biomarker] is one of the strongest predictors of prognosis,” Dr. Patel says.
Once your provider knows your IDH status, additional markers, such as 1p/19q and ATRX, can help your care team confirm they have identified the correct tumor type before recommending treatment.
MGMT Methylation
MGMT is a gene that helps tumors repair DNA damage, including damage caused by chemotherapy. If your tumor has MGMT, chemotherapy may be a less-effective treatment, Nduom says. But if the tumor has MGMT methylation, the tumor cells can’t fix themselves as easily, and chemotherapy may be more effective, he says.
TERT Promoter
TERT promoter mutations help tumors grow faster and resist treatments, and they’re often found in glioblastoma, Nduom says. This biomarker can help your doctor with a prognosis and diagnosis of your tumor.
“[But] we do not make any changes to our treatment based on the presence or absence of TERT promoter mutation,” he says.
EGFR Amplification
The epidermal growth factor receptor (EGFR) is a gene that helps control cell growth. When it is amplified, or there are extra copies of it, it can promote glioblastoma growth.
“Currently, there are no EGFR-inhibitors (also known as targeted therapy) that have been FDA-approved for use in glioblastoma,” says Santos, adding that clinical trials are underway on oral chemotherapy options for people with this mutation.
Mismatch Repair
Mismatch repair (MMR) deficiency is when your cells have a difficult time noticing errors when they duplicate themselves, which creates mutations, Nduom says.
“Although also a marker of tumor aggressiveness, having a lot of mutations in the tumor can be good for treatment,” he says, because the immune system may have an easier time recognizing these tumors as abnormal, which can make immunotherapy more effective.
BRAF Mutations
BRAF genes help send signals important to cell development, and BRAF mutations can indicate epithelioid glioblastoma — a rare and aggressive type of glioblastoma. These mutations aren’t common, but they can be a reason to consider targeted therapies such as BRAF or MEK inhibitors, Nduom says. Medications in this class include vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi).
Ki-67 Labeling Index
Ki-67, a protein biomarker, shows how fast a tumor is growing, Patel says. This biomarker can help predict how well treatment might work, and some research has found a connection between high Ki-67 levels and lower survival rates.
Mesenchymal Epithelial Transition Proto-Oncogene
Rarely, glioblastoma can include high levels of mesenchymal epithelial transition proto-oncogene (MET). High MET levels promote the formation and spread of glioblastoma cancer cells.
Neuron-Glial Antigen 2
Neuron-glial antigen 2 (NG2) is a protein found on the surface of certain brain cells. In a healthy brain, it plays a role in cell growth and repair. When NG2 shows up on a glioblastoma pathology report, it can indicate faster tumor growth and greater resistance to treatment.
Hyaluronic Acid Receptor CD44
Hyaluronic acid receptor CD44 (CD44) is similar to NG2 and can be a big factor in a tumor’s growth and potential to spread to other tissues. High CD44 levels are linked to lower survival rates, though CD44 is not usually one of the main biomarkers that guide glioblastoma treatment.
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