Urinary Biomarkers Show Promise in Diagnosing Brain Tumors

Caroline Cassels

May 06, 2008

May 6, 2008 (Chicago, Illinois) — Urinary biomarkers are showing promise as an effective, noninvasive way of detecting the presence or recurrence of brain tumors, a new pilot study suggests.

Presented at the American Association of Neurological Surgeons 76th Annual Meeting, the study's preliminary results indicate elevated levels of urinary matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be useful biomarkers for central nervous system (CNS) tumors, with a combined specificity and sensitivity of greater than 95% compared with controls.

"It's very early, but we were encouraged by the fact that MMP-related proteins can be detected in the urine of patients with CNS tumors and that we can trace them all the way back to the primary tumors, which we believe are the source of these markers," study investigator Edward R. Smith, MD, from Children's Hospital Boston, in Massachusetts, told conference attendees.

Currently, said Dr. Smith, there are no generally accepted screening protocols for the discovery of asymptomatic brain tumors, particularly primary brain tumors.

Further, he pointed out that despite recent advances in the imaging and treatment of brain tumors, the ability to prospectively diagnose new tumors or to detect tumor recurrence remains poor.

He added that early detection of tumors in other organ systems, both novel and recurrent, has frequently resulted in marked improvement in patient outcomes, a result he hopes to emulate in brain tumor patients.

Role in Angiogenesis

According to Dr. Smith, as tumors grow, they need to recruit blood vessels to sustain them, which requires remodeling of the extracellular matrix (ECM), and MMPs aid in this process.

These molecules, he added, all of which are secreted in the tumors themselves, end up in the systemic circulation, go into the kidneys, and ultimately end up in the urine.

Previous research has shown the presence of MMPs in the urine of patients with cancers in other organ systems, including breast and colon cancer. These findings led the researchers to consider whether they may also be present in the urine of brain tumor patients.

To determine whether urine testing could distinguish between individuals with brain tumors and those without the disease, investigators recruited a total of 28 pediatric and adult patients with nonmetastatic, primary glial and other primary CNS tumors.

Cerebrospinal fluid (CSF) and urine samples from the patients were analyzed for MMP-2, MMP-9, VEGF, and MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) and compared with those of 23 age- and sex-matched controls.

"There are a lot of other proteins we could have looked at, but we picked these 4 because we knew they were home runs in other organ systems," said Dr. Smith.

Holy Grail


The study showed statistically significant differences between the patients with tumors and controls. Specifically, the researchers found that MMP-2 and VEGF as stand-alone markers at 300 pg in urine had sensitivities and specificities between 82% and 95% or 89% and 95%, respectively. When combined, the 2 markers had a sensitivity and specificity of greater than 95%.

When the researchers looked to see whether there were any differences in MMP levels in children vs adults, they still found there was a statistically significant difference in patients vs controls, regardless of age.

MMP levels in CSF mirrored those found in the urine, a finding that Dr. Smith said, suggests the tumor is the source of the biomarkers. The investigators also looked to see whether biomarker levels changed after tumor removal.

"We looked at patients longitudinally and when the tumor was present, the markers were present. But when we took the tumor out and looked at them a year later, the markers go away, again adding further evidence that the tumor is the source of the markers," said Dr. Smith.

Further research to replicate these findings in a larger population is required. However, he said, the preliminary results are encouraging.

"The holy grail would be to have a urine test that we could use as an early screen to detect these tumors and their recurrence. My hope is that at some point we'll be able to achieve that," he said.

Dr. Smith has no relevant disclosures.

American Association of Neurological Surgeons 76th Annual Meeting: Abstract 629. Presented April 28, 2008.


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