The combination of PTEN deletion and 16p13.3 gain in prostate cancer provides additional prognostic information in patients treated with radical prostatectomy

摘要

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: 1.814.98; P<0.0001) and further stratified patients with low and intermediate risk of biochemical recurrence [Gleason grade group 12 (3+4), Gleason grade group 2 (3+4), pT2, prostate-specific antigen10, low and intermediate CAPRA-S score; log-rank P0.007]. 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: 2.1210.42; 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.