March 2, 2007

Study seeks new prostate cancer screening tools

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Neil Bhowmick, Ph.D., and colleagues are using proteomics technologies to identify biomarkers for prostate cancer diagnosis. (photo by Susan Urmy)

Study seeks new prostate cancer screening tools

Simple urine dipsticks — like those used in pregnancy tests — may one day be effective tools for prostate cancer screening.

Vanderbilt-Ingram Cancer Center investigators have used mass spectrometry technology to identify proteins in urine that distinguish prostate cancer from two other diseases of the prostate. Their findings, published Feb. 16 in Biochemical and Biophysical Research Communications, suggest that the technology will be useful for discovering additional biomarkers for prostate cancer diagnosis.

Prostate cancer remains the second most common cancer diagnosed in the United States, behind skin cancer in men. To date, the most widely used screening tools for prostate cancer are the digital rectal exam and blood levels of prostate specific antigen (PSA).

The problem with PSA screening is its high false positive rate, said Neil Bhowmick, Ph.D., assistant professor of Urologic Surgery and Cancer Biology. High levels of PSA do not necessarily mean that a man has prostate cancer.

“PSA doesn't distinguish other prostate diseases, like benign prostatic hyperplasia (enlarged prostate) or prostatitis (inflammation of the prostate), from prostate cancer,” Bhowmick said. “The others cause symptoms, but they aren't likely to kill the patient.”

A patient with high PSA levels is advised to have a biopsy. If a pre-cancerous condition called high-grade prostate intraepithelial neoplasia (HGPIN) is detected, the patient may enter into a cycle of PSA testing and repeated biopsies.

Bhowmick and a highly collaborative multi-disciplinary group sought to “find something better than PSA,” he said.

They screened 407 urine samples from two populations of men — one group seeking a diagnostic prostate biopsy in response to a suspicious PSA test or digital rectal exam, and a second group of men with prostate cancer compared to men without a history of prostate cancer.

Using a mass spectrometry technology called MALDI to screen the urine samples, the investigators zeroed in on and identified peptides that distinguished prostate cancer from HGPIN from benign prostatic hyperplasia, based on biopsy results.

“What is unique about this work is that we were not only able to differentiate patients with cancer from those with a benign condition, but we were also able to differentiate patients with cancer from those with the pre-neoplastic condition HGPIN,” Bhowmick said.

“That's something that PSA doesn't do, and there isn't anything available that does that.”

Bhowmick and colleagues identified two proteins — uromodulin and semenogelin — that have also been found to have altered expression in other cancers.

“It was reassuring that these proteins appear to have clinical significance, and we plan to pursue these as future diagnostics, in combination with PSA and other biomarkers that are being identified,” he said.

Bhowmick stressed that this type of project — large-scale biomarker discovery — required multi-disciplinary collaboration between urologists, clinical and research nurses, mass spectrometry experts, database developers, statisticians, biochemists, and cancer biologists.

The research was supported almost entirely by philanthropic donations, Bhowmick added.

The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation funded the initial efforts, and Susan and Luke Simons contributed personally to the project and organized additional donations from others in the Nashville community.