Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer - PubMed (original) (raw)

. 2013 Jun 25;108(12):2582-9.

doi: 10.1038/bjc.2013.248. Epub 2013 May 21.

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. 2013.

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).

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