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. 2013 Jun 25;108(12):2582-9.
doi: 10.1038/bjc.2013.248. Epub 2013 May 21.

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

J Cuzick  1 , Z H Yang, G Fisher, E Tikishvili, S Stone, J S Lanchbury, N Camacho, S Merson, D Brewer, C S Cooper, J Clark, D M Berney, H Møller, P Scardino, Z Sangale; Transatlantic Prostate Group
Collaborators, Affiliations

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

J Cuzick et al. Br J Cancer. .

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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Figures

Figure 1
Figure 1
Consort diagram: PTEN cohort derivation.
Figure 2
Figure 2
Prostatic adenocarcinoma showing PTEN-deficient (A) and PTEN-positive (B) staining by immunohistochemistry.
Figure 3
Figure 3
Univariate hazard ratios (95% CI) for PTEN IHC loss according to Gleason score (<7, =7 and >7), PSA (⩽10, 10–25 and >25 (ng ml−1)), Ki-67 (⩽5% and >5%), extent of disease (<21% and ⩾21%) and risk groups based on the clinical score (score<median, median<score<75% quantile, score >75% quantile). N, D and L denote the number at risk, deaths and PTEN loss counts in each subgroup.
Figure 4
Figure 4
Kaplan–Meier survival curves for PTEN IHC loss and normal PTEN divided by the median clinical score (low and high).
Figure 5
Figure 5
Histogram of the (normalised) clinical score based on the multivariate model using Gleason score, PSA, Ki-67 and extent of disease. The shaded area of each bar denotes the deaths in each clinical score bin. The arrows indicate the median score (36) and interquartile range (13–60).
See this image and copyright information in PMC

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