Genetic abnormalities predict prostate cancer survival

22 February 2010

The combination of three genetic abnormalities significantly impacts how long a prostate cancer patient is likely to survive with the disease, according to scientists at the Institute of Cancer Research (ICR).

The scientists believe that patients could be tested for these genetic abnormalities to help decide the intensity of treatment they should receive.

The team used a technique called fluorescence in situ hybridisation (FISH) to examine three specific genetic alterations in prostate cancer samples from 308 patients: loss of the PTEN gene and rearrangement of the ERG or ETV1 genes.

Previous studies have shown that ERG gene rearrangements occur commonly in prostate cancer as do deletions of all or part of the PTEN gene, but the combined impact of these abnormalities on survival in a large group of patients has not previously been examined.

Study lead author and ICR scientist Dr Alison Reid says the presence or absence of these abnormalities has a major impact on a patient’s risk of dying from prostate cancer.

“In this study, we found that patients who had none of these genetic alterations had a good prognosis — 85.5% were still alive after 11 years,” Dr Reid says. “Happily, the majority of prostate cancer sufferers in this study, 54%, were in this category.”

“But the prognosis was unfortunately much worse for the 6% of patients who had lost the PTEN gene but had neither an ERG nor ETV1 gene rearrangement. These patients had a much higher risk of dying from prostate cancer; long-term follow-up showed only 13.7% were still alive after 11 years.

“Our findings suggest that men diagnosed with prostate cancer could be tested for all three genetic alterations, and this information could be used to help determine how aggressively they should be treated.”

Testing for only one of the genetic abnormalities was not sufficient to predict survival, the scientists found, as it was the combination of alterations that was important.

Study senior co-author and head of the Everyman Male Cancer Campaign Professor Colin Cooper, on behalf of the Transatlantic Prostate Group, says prostate cancer is the most common cancer in men and the second highest cause of male cancer-related deaths in the Western world.

“Some prostate cancers grow so slowly that they never require treatment while others are aggressive and can be fatal,” Professor Cooper says. “There is an urgent need to find biological markers like these that will help us distinguish between the two groups of patients. Such a test could help us determine who requires radical, immediate treatment and who can receive less therapy and therefore be at lower risk of side-effects.”

Dr Helen Rippon, Head of Research at The Prostate Cancer Charity, says a test could be particularly critical in cases where traditional indicators — such as the grade of the tumour — suggest that urgent treatment may not be necessary.

"The next stage will be to do a prospective clinical trial using the new test to identify men with a poor prognosis and select them for aggressive treatment. Such a study would determine whether testing in this way really can improve survival rates," she says.

About the study

The research, published in the British Journal of Cancer, was a collaboration between the ICR and Jack Cuzick, the John Snow Professor of Epidemiology at Wolfson Institute of Preventive Medicine, Queen Mary University of London. Other contributing organisations include The Royal Marsden NHS Foundation Trust, The Orchid Tissue Bank at Barts and the London School of Medicine and Dentistry, Royal Liverpool University Hospital and Thames Cancer Registry at King’s College London in the UK, and Ruprecht-Karls-Universitat in Germany and Memorial Sloan-Kettering Cancer Centre in the US.

The study was funded by the National Cancer Research Institute, The Prostate Cancer Charity, The Grand Charity of Freemasons, The Rosetrees Trust, The Bob Champion Cancer Trust and The Royal Marsden Clinical Research Fund, while individual authors on the paper received funding from The Orchid Appeal, Cancer Research UK, the Medical Research Council and Prostate Cancer Research Foundation.


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