Personalized Treatment for Medulloblastoma Aided by New Antibody Diagnostic

Brain cancer, artwork
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A collaboration of international researchers has developed a simple antibody-based test that can help diagnose the childhood brain cancer medulloblastoma and also work out which patients are likely to need more intense therapy.

Medulloblastoma affects almost two people per million per year. It is ten times more common in children than adults and is the second most frequent brain tumor in children. Prognosis varies from very good to poor, depending a lot on the specific cancer type.

Within the four different types of medulloblastoma –WNT/β-catenin, Sonic Hedgehog, Group 3, and Group 4– there are a variety of known molecular subgroups that influence prognosis. For example, within groups 3/4 there are eight molecular subgroups recognized by the WHO.

“However, very few clinical centers worldwide possess the technical capabilities to determine DNA-methylation profiles or other molecular parameters of high-risk,” write the researchers in the journal Clinical Cancer Research. This means that many children diagnosed with medulloblastoma currently get the same treatment regardless of the subtype they have, which can lead to unnecessary toxic side effects in children with less aggressive forms of the condition.

To try and make it easier to stratify children with the condition into the best treatment groups and predict their prognosis better, researchers at the University of British Columbia and British Columbia Children’s Hospital Research Institute, along with international collaborators in Germany, the U.S. and Russia, have developed a simpler test using an antibody-based technique called immunohistochemistry.

“By using a technique that is available in virtually all clinical labs, our new test has the potential to improve the diagnosis and future treatment of medulloblastoma for children in almost every corner of the planet,” says the study’s lead author Alberto Delaidelli, a PhD candidate in the lab of Poul Sorensen, a professor of pathology and laboratory medicine at the University of British Columbia’s faculty of medicine.

After doing various transcriptomic and proteomic tests, the team identified a protein –TPD52— that was present at higher levels in children with a more severe subtype of the disease. The test was validated in a group of 387 children with type 3 or 4 medulloblastoma.

Getting a positive result for TPD52 on the immunohistochemistry test was a significant independent predictor of early relapse and death increasing risk by at least 3.6-fold. Notably, a positive test for this protein increased the risk of chemotherapy failing more than 12 times.

Adding the TPD52 test to other clinical measures also helped to more accurately classify the subtype of cancer that each child had in around half of the cohort.

“With this new test, more doctors may one day be able to identify children with the most aggressive forms of medulloblastoma and better tailor treatment,” says Sorensen, the study’s senior author.

The research team is now evaluating the test further in a clinical trial based in Germany to further assess its accuracy.

“Since integration of TPD52 immunohistochemistry in classification algorithms significantly improved outcome prediction, this test could be rapidly adopted for risk stratification on a global scale, independently of advanced but technically challenging molecular profiling techniques,” they conclude.

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