PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer

Abstract

BackgroundPTEN is the most commonly deleted tumor suppressor gene in primary prostate cancer (PCa) and its loss is associated with poor clinical outcomes and ERG gene rearrangement. ObjectiveWe tested whether PTEN loss is associated with shorter recurrence-free survival (RFS) in surgically treated PCa patients with known ERG status. Design, setting, and participantsA genetically validated, automated PTEN immunohistochemistry (IHC) protocol was used for 1275 primary prostate tumors from the Canary Foundation retrospective PCa tissue microarray cohort to assess homogeneous (in all tumor tissue sampled) or heterogeneous (in a subset of tumor tissue sampled) PTEN loss. ERG status as determined by a genetically validated IHC assay was available for a subset of 938 tumors. Outcome measurements and statistical analysisAssociations between PTEN and ERG status were assessed using Fisher's exact test. Kaplan-Meier and multivariate weighted Cox proportional models for RFS were constructed. Results and limitationsWhen compared to intact PTEN, homogeneous (hazard ratio [HR] 1.66, p=0.001) but not heterogeneous (HR 1.24, p=0.14) PTEN loss was significantly associated with shorter RFS in multivariate models. Among ERG-positive tumors, homogeneous (HR 3.07, p<0.0001) but not heterogeneous (HR 1.46, p=0.10) PTEN loss was significantly associated with shorter RFS. Among ERG-negative tumors, PTEN did not reach significance for inclusion in the final multivariate models. The interaction term for PTEN and ERG status with respect to RFS did not reach statistical significance (p=0.11) for the current sample size. ConclusionsThese data suggest that PTEN is a useful prognostic biomarker and that there is no statistically significant interaction between PTEN and ERG status for RFS. Patient summaryWe found that loss of the PTEN tumor suppressor gene in prostate tumors as assessed by tissue staining is correlated with shorter time to prostate cancer recurrence after radical prostatectomy.