Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer

on behalf of the Transatlantic Prostate Group(Queen Mary University of London), Jack Cuzick(Queen Mary University of London), Zi Yang(Queen Mary University of London), Gabrielle Fisher(Queen Mary University of London), Eliso Tikishvili(Myriad Genetics), Steven Stone(Myriad Genetics), Jerry S. Lanchbury(Institute of Cancer Research), Niedzica Camacho(Institute of Cancer Research), Sue Merson(Institute of Cancer Research), Daniel S. Brewer(University of East Anglia), Christopher S. Cooper(University of East Anglia), J Clark(University of East Anglia), Daniel M. Berney(Queen Mary University of London), Henrik Møller(Memorial Sloan Kettering Cancer Center), Peter T. Scardino(Memorial Sloan Kettering Cancer Center), Zaina Sangale(Myriad Genetics)
British Journal of Cancer
May 21, 2013
Cited by 102Open Access
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Abstract

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict. We report on the prognostic value of phosphatase and tensin homologue (PTEN) loss in a cohort of 675 men with conservatively managed prostate cancer diagnosed by transurethral resection of the prostate. METHODS: The PTEN status was assayed by immunohistochemistry (PTEN IHC) and fluorescent in situ hybridisation (PTEN FISH). The primary end point was death from prostate cancer. RESULTS: The PTEN IHC loss was observed in 18% cases. This was significantly associated with prostate cancer death in univariate analysis (hazard ratio (HR)=3.51; 95% CI 2.60-4.73; P=3.1 × 10(-14)). It was highly predictive of prostate cancer death in the 50% of patients with a low risk score based on Gleason score, PSA, Ki-67 and extent of disease (HR=7.4; 95% CI 2.2-24.6; P=0.012) ), but had no prognostic value in the higher risk patients. The PTEN FISH loss was only weakly associated with PTEN IHC loss (κ=0.5). Both PTEN FISH loss and amplification were univariately predictive of death from prostate cancer, but this was not maintained in the multivariate analyses. CONCLUSION: In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease.


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