Urinary = Biomarkers Show Promise in Diagnosing Brain Tumors

http://www.medscape.com/ =

To Print: Click = your browser's=20 PRINT button.

NOTE: To view = the article=20 with Web enhancements, go to:
http://www.medscape.c= om/viewarticle/574066

Urinary Biomarkers Show Promise in Diagnosing = Brain=20 Tumors

Caroline Cassels

Medscape Medical News 2008. =A9 2008 Medscape

May 6, 2008 (Chicago, = Illinois) =97=20 Urinary biomarkers are showing promise as an effective, = noninvasive way of=20 detecting the presence or recurrence of brain tumors, a new pilot = study=20 suggests.

Presented at the American Association of Neurological Surgeons = 76th=20 Annual Meeting, the study's preliminary results indicate elevated = levels=20 of urinary matrix metalloproteinases (MMPs) and vascular = endothelial=20 growth factor (VEGF) may be useful biomarkers for central nervous = system=20 (CNS) tumors, with a combined specificity and sensitivity of = greater than=20 95% compared with controls.

"It's very early, but we were encouraged by the fact that = MMP-related=20 proteins can be detected in the urine of patients with CNS tumors = and that=20 we can trace them all the way back to the primary tumors, which we = believe=20 are the source of these markers," study investigator Edward R. = Smith, MD,=20 from Children's Hospital Boston, in Massachusetts, told conference = attendees.

Currently, said Dr. Smith, there are no generally accepted = screening=20 protocols for the discovery of asymptomatic brain tumors, = particularly=20 primary brain tumors.

Further, he pointed out that despite recent advances in the = imaging and=20 treatment of brain tumors, the ability to prospectively diagnose = new=20 tumors or to detect tumor recurrence remains poor.

He added that early detection of tumors in other organ systems, = both=20 novel and recurrent, has frequently resulted in marked improvement = in=20 patient outcomes, a result he hopes to emulate in brain tumor = patients.=20

Role in Angiogenesis

According to Dr. Smith, as tumors grow, they need to recruit = blood=20 vessels to sustain them, which requires remodeling of the = extracellular=20 matrix (ECM), and MMPs aid in this process.

These molecules, he added, all of which are secreted in the = tumors=20 themselves, end up in the systemic circulation, go into the = kidneys, and=20 ultimately end up in the urine.

Previous research has shown the presence of MMPs in the urine = of=20 patients with cancers in other organ systems, including breast and = colon=20 cancer. These findings led the researchers to consider whether = they may=20 also be present in the urine of brain tumor patients.

To determine whether urine testing could distinguish between=20 individuals with brain tumors and those without the disease, = investigators=20 recruited a total of 28 pediatric and adult patients with = nonmetastatic,=20 primary glial and other primary CNS tumors.

Cerebrospinal fluid (CSF) and urine samples from the patients = were=20 analyzed for MMP-2, MMP-9, VEGF, and MMP-9/neutrophil=20 gelatinase-associated lipocalin (NGAL) and compared with those of = 23 age-=20 and sex-matched controls.

"There are a lot of other proteins we could have looked at, but = we=20 picked these 4 because we knew they were home runs in other organ=20 systems," said Dr. Smith.

Holy Grail

The study showed statistically significant differences between = the=20 patients with tumors and controls. Specifically, the researchers = found=20 that MMP-2 and VEGF as stand-alone markers at 300 pg in urine had=20 sensitivities and specificities between 82% and 95% or 89% and = 95%,=20 respectively. When combined, the 2 markers had a sensitivity and=20 specificity of greater than 95%.

When the researchers looked to see whether there were any = differences=20 in MMP levels in children vs adults, they still found there was a=20 statistically significant difference in patients vs controls, = regardless=20 of age.

MMP levels in CSF mirrored those found in the urine, a finding = that Dr.=20 Smith said, suggests the tumor is the source of the biomarkers. = The=20 investigators also looked to see whether biomarker levels changed = after=20 tumor removal.

"We looked at patients longitudinally and when the tumor was = present,=20 the markers were present. But when we took the tumor out and = looked at=20 them a year later, the markers go away, again adding further = evidence that=20 the tumor is the source of the markers," said Dr. Smith.

Further research to replicate these findings in a larger = population is=20 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=20 early screen to detect these tumors and their recurrence. My hope = is that=20 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.