A Prospective Study Assessing the Predictive Value of TMPRSS2-ERG Gene Fusion and PTEN Deletion in High Risk Prostate Cancer Patients
One of the biggest problems facing prostate cancer patients and their treating physicians is
who needs to be treated and when. Common clinical and pathological parameters are useful
(PSA, Gleason score, etc.) but do not clearly predict who will benefit from treatment and
who will fail. Genetic markers for tumour aggressivity would be of greater value. The finding
that the TMPRSS2-ERG gene fusion is associated with an increase risk of cancer progression
is important. TMPRSS2 is controlled by androgen (testosterone) and ERG is part of a family
of proteins which have a role in controlling cell growth, cell specialization and producing
tumours. As a consequence of this gene fusion, production of the ERG protein increases in the
presence of testosterone and could be key to the development of prostate cancer, resistance
to treatment and poor outcome. The PTEN gene is known to have a role as a tumour suppressor.
Its deletion is a contributing factor in the development of prostate cancers and poor
outcome. The coexistence of the two markers could be associated with a higher risk of
To date there have been no studies regarding the presence of either of these two markers or
their coexistence in high risk prostate cancer patients who, despite radiation therapy and
androgen suppression, develop biochemical failure (their PSA levels rise once again).
Patients participating in the PCS IV study (high risk prostate cancer treated with radiation
therapy plus either 18 or 36 months of hormonal suppression) who have had biochemical
failure or 3 years of follow-up post hormonal therapy will be approached.
Tumour blocks from consenting patients will be collected and analyzed for the presence of the
TMPRSS2-ERG gene fusion and the PTEN deletion at the Pathology Department of the Jewish
General Hospital. Statistical analysis will be carried out to see whether either or both
markers are present, whether they are associated with certain clinical and pathological high
risk factors, and whether they can be used to predict which patients will fail treatment.
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