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