Negative LC3b immunoreactivity in cancer cells is an independent prognostic predictor of prostate cancer specific death
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Ashkan Mortezavi1, Souzan Salemi1, Niels J. Rupp2, Jan Hendrik Rüschoff2, Thomas Hermanns1, Cedric Poyet1, Marco Randazzo1, Hans-Uwe Simon3, Holger Moch2, Tullio Sulser1, Peter Wild2 and Daniel Eberli1
1Department of Urology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
2Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
3Institute of Pharmacology, Inselspital, University of Bern, 3010 Bern, Switzerland
Daniel Eberli, email: Daniel.Eberli@usz.ch
Keywords: autophagy, LC3b, prostate cancer, biochemical recurrence, survival
Received: August 29, 2016 Accepted: February 20, 2017 Published: March 07, 2017
Background: Autophagy is a catabolic cellular process used for degradation of cytoplasmic organelles and preservation of cell viability. In this study we aimed to analyse the level of autophagy markers in benign and malignant prostate tissue and to evaluate the prognostic properties for patients with prostate cancer (PCa).
Results: LC3b expression was significantly upregulated in PCa, especially in metastatic and castration-resistant PCa samples compared to benign prostate tissue (p<0.001). Evaluation of expression in malignant radical prostatectomy specimens revealed an inverse association with preoperative serum PSA levels (p=0.02) and Gleason Score (p=0.07). LC3b immunoreactivity was identified as a novel predictor of PCa specific death after radical prostatectomy, independent of Gleason score, tumour stage, and surgical margin status in a multivariable cox regression analysis (hazard ratio 0.09, 95% confidence interval 0.01-0.69, p=0.021). A significant association of ATG-5 and Beclin 1 with LC3b expression could be noticed (p<0.001), but no link with other clincopathologic parameters was observed.Materials and
Methods: A Tissue microarray containing 468 formalin-fixed, paraffin-embedded prostate tissue cores was stained immunohistochemically for major autophagy proteins LC3b, ATG5 and Beclin 1. Immunoreactivity was semiquantitatively scored and correlated with pathologic and clinical parameters, including tumour stage, Gleason score, preoperative PSA level, biochemical recurrence rate and survival. The median clinical follow-up was 132 months.
Conclusion: LC3b was significantly overexpressed in malignant compared to benign prostate tissue. However, positive LC3b immunoreactivity in PCa, as a marker of increased autophagy, was independently associated with a reduced disease-specific mortality.
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