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Could just three genes identify potentially lethal prostate cancer?

Posted Jan 26 2010 12:00am

A new report from members of the Transatlantic Prostate Study Group has suggested that information about three specific genes may be sufficient to identify a high proportion of men with potentially lethal as opposed to indolent prostate cancer.

Reid et al. set out to evaluate the potential clinical significance and the natural history of different categories of prostate cancer by combining information about rearrangements of the ERG/ETV1 genes and loss of the PTEN gene in 308 prostate cancer patients who were conservatively managed and for whom survival and other outcome data were available. They used a well-known technique known as fluorescence in situ hybridization (FISH) to detect PTEN gene loss and ERG/ETV1 gene rearrangements in DNA from the patients’ prostate cancer specimens.

The results of this study showed that:

  • On their own, neither ERG/ETV1 gene rearrangements nor PTEN gene loss demonstrated any link to long-term survival in multivariate analyses.
  • In general, there was a strong association between ERG/ETV1 gene rearrangements and PTEN gene loss (P < 0.001); in other words, if a patient had lost the PTEN gene, he tended to have ERG/ETV1 gene rearrangements (and vice versa).
  • 54 percent of patients, who showed no signs of either PTEN gene loss or ERG/ETV1 gene rearrangements comprised a “good prognosis” population with a high level of favorable cancer-specific survival (85.5 percent survival at 11 years).
  • The loss of the PTEN gene without any indication of ERG/ETV1 gene rearrangements identified a subset of 6 percent of the patients who had significantly greater risk for prostate cancer-specific mortality (only 13.7 percent survival at 11 years) when compared with the “good prognosis” group.

As we state regularly in reporting on studies of this type, what the authors have shown here is a strong “association” between the lack of ERG/ETV1 gene rearrangements, loss of the PTEN gene, and prostate cancer-specific mortality. What is going to be needed next is a prospective study that will allow us the clearly establish whether loss of the PTEN gene but the absence of ERG/ETV1 gene rearrangements offers a prognostic tool that can accurately predict risk for progressive disease and prostate cancer-specific mortality in a carefully identified group of patients who have chosen to be managed using active surveillance or some other conservative treatment protocol.

The “New” Prostate Cancer InfoLink does feel that this methodology, which employs well-understood FISH technology, might be easily developed into an accurate prognostic method to differentiate between men with indolent and potentially lethal forms of prostate cancer — if it can be validated in future clinical trials. FISH technology is already used regularly to identify women with breast cancer who express the HER2/neu gene and who are therefore appropriate candidates for treatment with trastuzumab (Herceptin).

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