New technique to test for deadliest prostate tumours

Steve Connor
Wednesday 09 October 2002 19:00 EDT
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A test for the most aggressive form of prostate cancer – which kills about 9,500 men in the UK each year – has come a step closer with a study showing that a technique can detect whether a tumour of the prostate gland is potentially lethal.

Scientists have identified a human gene that is closely linked with whether a prostate tumour will spread to other parts of the body.

The researchers discovered the role of the gene by using RNA interference (RNAi), a new technique that allows scientists to block any given gene. When RNAi was used on prostate cancer cells in a test tube they died within days.

If the gene is active then the cancer appears destined to become metastatic, when it spreads irreversibly from the prostate gland to other organs and tissues such as the bone. A prototype test has shown a way of determining whether a prostate cancer is likely to become metastatic, suggesting it may soon be possible to identify those patients who need to have radical surgery or aggressive treatment to prevent the tumour from spreading.

A team of scientists led by Arul Chinnaiyan, assistant professor of pathology and urology at the University of Michigan in Ann Arbor, developed the rudimentary test by studying more than 1,000 tissue samples from hundreds of prostate cancer patients.

In a study published in the journal Nature the scientists say that when the gene, known as EZH2, is actively "expressed" it appears to suppress other genes that are involved in preventing the progression of prostate cancer.

"We found the greatest EZH2 overexpression in metastatic prostate cancer tissue. At this point, it's unclear whether the gene plays a role in cancer's development or is simply an indicator of lethal progression," Professor Chinnaiyan said.

The breakthrough is the first time scientists have found a significant "marker" to indicate whether a prostate tumour is potentially lethal and it could help doctors to make decisions on how to deal with a patient with prostate cancer. "It allows us to distinguish between those patients where it would be more appropriate to watch and wait and those that should be treated aggressively," Professor Chinnaiyan said.

Prostate cancer cells usually carried on dividing in the test tube but when the EZH2 gene was blocked by the RNAi technique there was a dramatic reversal in progression, he said.

"The first thing we noticed is that the cells stopped growing. After 120 hours, 80 per cent to 90 per cent of the cultured cells containing the RNA nucleotides [molecules] targeted for EZH2 had stopped dividing," Professor Chinnaiyan said.

"When cells can't divide and grow, they die. This suggests that EZH2 could play an important role in the progression of prostate cancer."

The success of RNAi in test-tube studies suggests that the technique could also be used for treatment, according to Mark Rubin, a leading member of the American team.

"Over the past 50 years, there has been no significant improvement in clinical outcome for men diagnosed with advanced prostate cancer and no way to tell ahead of time which cancers will spread and which cancer will remain localised," Dr Rubin said.

In Britain, there are more than 21,700 new cases of the disease each year, making it the second most common form of cancer in the UK, with each man having a one-in-14 risk of developing prostate cancer.

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