Association of low PTEN expression by fluorescence immunohistochemistry (F-IHC) and lethal disease in men with surgically-treated prostate cancer (PrCa).

Abstract

15 Background: Loss of PTEN expression correlates with poorer clinical outcomes after definitive therapy for non-metastatic (M0) PrCa. While most studies have used biochemical-based end points, there is limited data regarding PTEN loss by IHC and risk of lethal disease after surgery. Methods: A retrospective cohort of patients who underwent radical prostatectomy (RP) was identified from the Dana-Farber Prostate Clinical Research Information Systems (CRIS) database. Formalin-fixed, paraffin-embedded RP specimens were used to construct tissue microarrays and F-IHC for PTEN was performed. Using multispectral imaging analysis, tumor-only PTEN expression was quantified. PTEN expression was analyzed continuously and dichotomously (low [ < lower quartile] vs other [≥lower quartile]). Kaplan-Meier method estimated the distribution of time from RP to metastatic disease and overall survival (OS). Cox model assessed association of PTEN status and the disease outcomes, with adjustment of age, Gleason score and pathological stage in multivariate analyses (MVA). Prognostic ability of PTEN was also explored using a logistic regression model. Results: The analysis cohort comprised 91 patients with either non-lethal (no metastatic or biochemical relapse) or lethal disease (metastasis post-RP). The median follow-up was 12.4 years. PTEN low was significantly associated with lethal disease as both a continuous (HR 1.82, 95% CI 1.35-2.44) and dichotomous (HR 2.94, 95% CI 1.52-5.56) variable. Significant association of PTEN-low expression and poorer OS was observed (cont: HR 2.22, 95% CI 1.54-3.23; low vs other: HR 4.00, 95% CI 1.89-8.33). MVA models yielded consistent results. A prognostic model assessing 10-year disease outcomes showed incremental prognostic improvement with PTEN status added to age/Gleason/stage (lethal disease: area under curve (AUC) 0.79 vs 0.84 [+PTEN status]; death: AUC 0.71 vs 0.76 [+PTEN status]). Conclusions: Low PTEN expression by F-IHC in primary prostate cancer is an independent prognostic biomarker of lethal disease and death after surgery. Quantitative F-IHC for PTEN is a viable diagnostic assay in this context.