A gene that is overexpressed in urothelial cells is a highly sensitive and specific cancer biomarker.
Counting copies of a specific gene in cells gathered from a urine sample may provide a simple, noninvasive way to detect bladder cancer, according to researchers at The University of Texas MD Anderson Cancer Center in Houston.
When the gene, Aurora kinase A (AURKA), is overexpressed in urothelial cells, errors during cell division follow. The new cells have too few or too many chromosomes instead of the usual 23 chromosome pairs.
“Abnormal chromosome counts are the most fundamental feature, the signature, of human cancers,” said senior study author Bogdan Czerniak, MD, PhD, a professor of pathology. “We have further clarified the role that AURKA plays in this misaggregation of chromosomes in bladder cancer. As a biomarker, AURKA can detect bladder cancer in voided urine with high degrees of sensitivity and specificity.” Study findings appear in Journal of The National Cancer Institute (2008;100;1401-1411).
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He and his colleagues used fluorescence in situ hybridization (FISH) to count copies of the gene in urothelial cells obtained from urine samples. A blinded analysis of samples from 23 bladder cancer patients and seven cancer-free controls showed that the AURKA biomarker identified all 23 cancer cases and correctly characterized six of the seven controls as not having bladder cancer.
The biomarker test was validated in urine samples from a separate group of 100 bladder cancer patients and 148 controls. Blinded analysis showed the biomarker accurately identified 87 of the cancer cases and characterized 96.6% of the controls as cancer-free, producing only five false positives.
Cytologic analysis was conducted on additional samples from 59 cancer cases. Microscopic examination of the cells identified 48 of the 59 cancers (81.4%). Nine of the 11 cases mischaracterized by cytology were correctly identified by the FISH test.
“It appears that the biomarker is better than cytologic analysis of cells isolated from urine,” Dr. Czerniak said. “Our next step is to develop an FDA-approved, commercially available test.”
That will require independent validation in prospective, multi-institutional clinical trials, however. If approved, the test could detect new and recurrent cases earlier, leading to increased bladder preservation and improved survival.
In a series of experiments that led to the urine tests, the researchers demonstrated that AURKA overexpression is tightly associated with chromosomal misaggregation, and both occur most profoundly in the most aggressive forms of bladder cancer.
AURKA encodes a protein important to orderly cell division and equal segregation of chromosomes. The protein is involved in the duplication, maturation, and distribution of centrosomes, which function during cell division to assure that each daughter cell receives the normal 23 pairs of chromosomes.
“We think if we combine tests, we will get better results,” Dr. Czerniak told Renal & Urology News. “This is highly unlikely to replace the currents tests, but this new urine test could greatly enhance the detection rate of bladder cancer during clinical workup.”
