173 Reduced autophagy levels are associated with a higher Gleason score, tumour stage and an increased rate of prostate cancer specific death

Abstract

INTRODUCTION AND OBJECTIVES: Autophagy is a catabolic cellular process used for degradation of cytoplasmic organelles and preservation of cell viability. Data regarding the role of autophagy in treatment naive prostate cancer (PCa) is sparse. Therefore we aimed to analyze the level of autophagy in benign and malignant prostate tissue and to evaluate the prognostic properties for patients with PCa. METHODS: A Tissue microarray containing 479 formalin-fixed, paraffin-embedded prostate tissue cores was stained immunohistochemically for major autophagy proteins ATG5, Beclin1 and LC3b: 41 normal prostate tissues, 382 primary adenocarcinomas (ADC) and 56 prostate cancer metastases or castration resistant prostate cancers. Immunoreactivity was semiquantitatively scored and correlated with pathologic and clinical parameters including survival. RESULTS: LC3b expression was significantly upregulated in PCa, especially in metastatic and castration-resistant prostate cancer samples compared to normal prostate tissue (p1⁄40.002). Evaluation of expression in ADCs revealed an inverse association with preoperative serum PSA level (p1⁄40.047), pT-stage (0.033) and Gleason Score (p1⁄40.026). Negative LC3b expression was identified as a novel predictor of prostate cancer specific death after radical prostatectomy (p1⁄40.02). A significant association of ATG-5 and Beclin1 with LC3b expression could be noticed, but no link with clincopathologic parameters. CONCLUSIONS: A lower LC3b expression in prostate cancer tissue is significantly associated with a higher rate of prostate cancer specific death. Furthermore, there is a significant association of a lower expression in tumors with extraprostatic extension and higher Gleason Scores. This is the first report evaluating autophagy expression levels and their association with the clinical course in prostate cancer patients.