Loss of PTEN Expression Detected by Fluorescence Immunohistochemistry Predicts Lethal Prostate Cancer in Men Treated with Prostatectomy

Abstract

Background: PTEN deletion is associated with relapse after therapy for localized prostate cancer. There are limited data on PTEN loss as detected by immunohistochemistry (IHC) and the risk of lethal disease after surgery.

Objective: To determine whether PTEN loss as detected by quantitative fluorescence IHC (FIHC) predicts lethal disease outcomes after surgery for prostate cancer.

Design, setting and participants: We used formalin-fixed, paraffin-embedded radical prostatectomy specimens to construct tissue microarrays and perform dual FIHC for PTEN and AMACR for masking tumor epithelium, plus semi-quantitative multispectral imaging analysis.

Outcome measurements and statistical analysis: The association of PTEN status analyzed continuously and dichotomously (low [expression in the lowest quartile] vs higher [expression >lowest quartile]) with disease outcomes (metastasis and death) was assessed with adjustment for age, Gleason score, and stage in multivariable analyses. The prognostic ability of PTEN was assessed using logistic regression models.

Results and limitations: Low PTEN expression was associated with a higher risk of metastatic disease as both a continuous (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.14-1.92; p<0.003) and dichotomous (HR 1.92, 95% CI 1.02-3.63; p=0.04) variable. A significant association between low PTEN expression and poorer overall survival was observed (continuous: HR 1.89, 95% CI 1.37-2.63; p<0.001; dichotomous: HR 2.66, 95% CI 1.34-5.28; p=0.005). Addition of PTEN status to clinicopathologic factors (age, Gleason score, and stage) incrementally improved a prognostic model assessing 10-yr outcomes for metastatic disease (area under the curve [AUC] 0.76 vs 0.80) and death (AUC 0.70 vs 0.75).

Conclusions: Low PTEN expression detected by FIHC in primary prostate cancer is an independent prognostic biomarker for metastatic disease and death after definitive therapy. FIHC for PTEN is a viable clinical diagnostic assay in this context.

Patient summary: We looked at loss of the PTEN protein in prostate tumors from men treated with surgery. Men with PTEN loss were at higher risk of metastasis and death. Assessing PTEN status may be useful in better determination of the risk of poorer outcomes.

Keywords: Immunofluorescence; Immunohistochemistry; PTEN; Prostate cancer; Prostatectomy.