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A New Biomarker for Bladder Cancer?By Joe Munch
Counting copies of the Aurora kinase A gene (AURKA) in exfoliated urothelial cells in voided urine may allow physicians to detect bladder cancer early, a team led by researchers at M. D. Anderson has found. Currently available noninvasive diagnostic tests do not reliably detect low-grade bladder cancers, and various benign conditions often result in false positives on these tests, according to Bogdan Czerniak, M.D., Ph.D., a professor in the Department of Pathology and the study’s senior author. While bladder cancers can be reliably detected by cystoscopy—an endoscopic procedure performed through the urethra—the procedure’s invasive nature limits its use to confirming suspected cancer. Counting the copies of AURKA, Dr. Czerniak said, “has the potential to be highly efficient because it actually tests for the marker that plays a major role in the development of certain key features of bladder cancer, like aneuploidy.” Aneuploidy—an abnormal number of chromosomes—is a fundamental feature of many human cancers. When the AURKA gene is overexpressed or amplified, as it is in many types of human cancers, it can contribute to the creation of an abnormal number of centrosomes, subsequent chromosomal missegregation, and ultimately aneuploidy during mitosis. As the level of AURKA rises, so does the frequency of aneuploidy. “All bladder cancers have some degree of amplification of AURKA, and the degree of this amplification correlates very well with the degree of malignancy,” Dr. Czerniak said. In their research, which was published in the Journal of the National Cancer Institute, Dr. Czerniak and his colleagues first conducted a functional study to confirm that the AURKA gene can missegregate chromosomes in urothelial cells. They found that forced AURKA expression increased the number of centrosomes and the occurrence of aneuploidy in human urothelial cells. Using fluorescence in situ hybridization, the team counted the AURKA gene copy number in exfoliated urothelial cells in urine samples from 23 bladder cancer patients and 7 healthy controls. Using the data, the team created a bladder cancer detection model that was then tested on a separate set of urine samples from 100 bladder cancer patients and 148 controls (92 healthy individuals and 56 patients with benign urologic disorders). According to Dr. Czerniak, the biomarker test detected bladder cancer with a high degree of specificity and reasonable sensitivity. More important, the test was able to detect bladder cancer at earlier stages than conventional methods, meaning that it could be used to identify cases that would otherwise be missed during an initial screening, leading to increased rates of bladder preservation and patient survival. The test could also be used to detect recurrences early. Additionally, said Dr. Czerniak, “It is a relatively simple test, so it can be performed in a regular hospital—a fluorescence microscope and simple laboratory devices are sufficient to conduct the test, so potentially it is applicable to a wide population of patients.” The test will not be ready for clinical application until it is approved by the U.S. Food and Drug Administration, which requires a multi-institutional validation trial. According to Dr. Czerniak, a commercial version of the test is “at least several years away.” And although the test, if approved, will probably not take the place of existing diagnostic tests for bladder cancer, Dr. Czerniak said, “We know that this test can complement cytology. And there is a pretty good chance that it will expand the diagnostic armamentarium used to detect bladder cancer.”For more information, contact Dr. Czerniak at 713-794-1025. Other articles in OncoLog, February 2009 issue:
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