Prostate cancer is a clinically heterogeneous disease and accurately risk-stratifying patients is a key clinical challenge. We hypothesized that the concurrent identification of the DNA copy number alterations 10q23. 3 (PTEN) deletion and 16p13.3 (PDPK1) gain, related to the PI3K/AKT survival pathway, would improve prognostication. We assessed PTEN deletion status using fluorescence in situ hybridization (FISH) and evaluated its clinical significance in combination with the 16p13.3 gain in a set of 332 primary radical prostatectomy cases on a tissue microarray with clinical follow-up. The PTEN deletion was detected in 34% (97/287) of the evaluable tumors and was significantly associated with high Gleason grade group (P < 0.0001) and advanced pathological tumor stage (pT-stage, P < 0.001). The PTEN deletion emerged as a significant predictor of biochemical recurrence independent of the standard clinicopathologic parameters (hazard ratio: 3.00, 95% confidence interval: 1.81-4.98; P < 0.0001) and further stratified patients with low and intermediate risk of biochemical recurrence [Gleason grade group 1-2 (≤3 + 4), Gleason grade group 2 (3 + 4), pT2, prostate-specific antigen ≤ 10, low and intermediate CAPRA-S score; log-rank P ≤ 0.007]. A PTEN deletion also increased the risk of distant metastasis (log-rank, P = 0.001), further supporting its role in prostate cancer progression. Combining both 16p13.3 gain and PTEN deletion improved biochemical recurrence risk stratification and provided prognostic information beyond the established CAPRA-S score (co-alteration: hazard ratio: 4.70, 95% confidence interval: 2.12-10.42; P < 0.0001). Our study demonstrates the potential clinical utility of PTEN genomic deletion in low-intermediate risk patients and highlights the enhanced prognostication achieved when assessed in combination with another genomic biomarker related to the PI3K/AKT pathway, thereby supporting their promising usefulness in clinical management of prostate cancer.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2018 Aug 23 [Epub ahead of print]
Yogesh M Bramhecha, Shaghayegh Rouzbeh, Karl-Philippe Guérard, Eleonora Scarlata, Fadi Brimo, Simone Chevalier, Lucie Hamel, Armen G Aprikian, Jacques Lapointe
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, QC, Canada., Department of Pathology, McGill University and the Research Institute of the McGill University Health Centre, Montreal, QC, Canada., Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, QC, Canada. .