Protein can predict progression of most common childhood brain tumor, UT Southwestern researchers find

DALLAS – July 28, 2003 – Researchers at UT Southwestern Medical Center at Dallas have discovered that the presence of a particular protein can predict whether the most common childhood brain tumor will continue to grow or return following surgery.

The tumor, pilocytic astrocytoma, is more likely to progress if large amounts of the Ki-67 antigen are present in cancer cells, suggesting that certain tumors are biologically predisposed to progress or reoccur, the UT Southwestern researchers report.

The study – one of the largest of its kind – appears in the August edition of the Journal of Clinical Oncology and goes online today. The findings were also presented at the American Society for Clinical Oncology meeting in June.

About 40 percent of all childhood brain tumors are pilocytic astrocytomas. Although not usually life threatening, the tumor can cause problems with speech, balance and coordination, walking and handling objects. About 1,100 children under 18 are diagnosed with pilocytic astrocytomas annually in the United States.

This latest discovery helps explain why some children’s brain tumors don’t return after surgery and others continue to grow. The finding also provides an important prognostic tool for doctors, said Dr. Daniel Bowers, assistant professor of pediatrics and lead author of the study.

“This finding already makes a difference in how we treat patients,” he said. Now he follows patients with high levels of MIB-1, an antibody that is immunoreactive with the Ki-67 antigen, more closely so that he can detect any potential relapse as early as possible.

MIB-1 is an important prognostic factor for certain malignant brain tumors in adults but has not been extensively studied in childhood pilocytic astrocytomas. Dr. Bowers said he has long suspected a connection.

“This report is the first real evidence that there’s more to the story,” he said.

Researchers looked at cell samples from 118 patients evaluated and treated in the neuro-oncology program of Children’s Medical Center of Dallas. Tumor cells were stained with the MIB-1 antibody. Researchers sampled the number of positive cells to determine the MIB-1 index, which is the percentage of positive cells compared to an estimate of the total number of cells.

Dr. Linda Margraf, associate professor of pathology and the study’s senior author, said that patients with more than 2 percent of positive cells had an increased risk of cancer recurrence or growth.

Dr. Margraf said the test, although time-consuming, is now available and could benefit children with a history of pilocytic astrocytomas. “Most pathology labs can do it, and it is available at most major medical centers,” she said.

The next step in the research is to identify genes that are overexpressed – or turned on – in progressive tumors. Researchers hope to one day define tumors genetically and create drugs to treat the problem.

Other UT Southwestern researchers who worked on the study included Dr. Payal Kapur, a pathology postdoctoral trainee; Dr. Joan Reisch, director of academic computing services and associate professor of family practice and community medicine; Dr. Arlynn Mulne, clinical instructor of pediatrics; Dr. Kenneth Shapiro, clinical associate professor of neurological surgery; Dr. Roy Elterman, clinical associate professor of neurology; and Dr. Naomi Winick, professor of pediatrics.

The study was supported by Children’s Medical Center Foundation, the Children’s Cancer Fund of Dallas and the Children’s Brain Tumor Foundation of the Southwest.

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Media Contact: Staishy Bostick Siem
214-648-3404
or e-mail: staishy.siem@utsouthwestern.edu

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