Alexandra Giatromanolaki1, Efthimios Sivridis2, Savvas Mendrinos3, Anastasios V Koutsopoulos2, Michael I Koukourakis4. 1. Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece. Electronic address: agiatrom@med.duth.gr. 2. Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece. 3. Division of Pathology Integrated Medical Professionals, New York, NY. 4. Department of Radiotherapy/Oncology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Abstract
OBJECTIVES: Up-regulation of autophagy provides an important survival mechanism to normal and malignant cells residing in a hypoxic and unfavorable nutritional environment. Yet, its role in the biology of prostate cancer remains poorly understood. METHODS: In this study we investigated the expression of four major autophagy proteins, namely the microtubule-associated protein 1 light chain 3A (LC3A), LC3B, Beclin 1, and p62, together with an enzyme of anaerobic metabolism, the lactate dehydrogenase 5 (LDH5), in relation to Gleason score and extraprostatic invasion. A series of 96 prostate adenocarcinomas was examined using immunohistochemical techniques and appropriate antibodies. RESULTS: The LC3A protein was expressed in the form of "stone-like" structures, and diffuse cytoplasmic staining, the LC3B reactivity was solely cytoplasmic, whereas that of p62 and LDH5 was both cytoplasmic and nuclear. A median count of 0.90 "stone-like" structures per 200 × optical field (range 0-3.6) was highly associated with a high Gleason score. Similarly, a strong cytoplasmic LC3A, LC3B, and p62 expression, when extensive (present in>50% tumor cells per section), was significantly associated with LDH5 and a high Gleason score. In addition, extensive cytoplasmic p62 expression was related with LC3A and B reactivity and also with extraprostatic invasion. Extensive Beclin-1 expression was significantly linked with extraprostatic invasion and also with p62 and LDH5 expression. CONCLUSIONS: Immunohistochemical detection of autophagy proteins may potentially prove to be useful as prognostic markers and a tool for the stratification of patients in therapeutic trials targeting autophagy in prostate cancer.
OBJECTIVES: Up-regulation of autophagy provides an important survival mechanism to normal and malignant cells residing in a hypoxic and unfavorable nutritional environment. Yet, its role in the biology of prostate cancer remains poorly understood. METHODS: In this study we investigated the expression of four major autophagy proteins, namely the microtubule-associated protein 1 light chain 3A (LC3A), LC3B, Beclin 1, and p62, together with an enzyme of anaerobic metabolism, the lactate dehydrogenase 5 (LDH5), in relation to Gleason score and extraprostatic invasion. A series of 96 prostate adenocarcinomas was examined using immunohistochemical techniques and appropriate antibodies. RESULTS: The LC3A protein was expressed in the form of "stone-like" structures, and diffuse cytoplasmic staining, the LC3B reactivity was solely cytoplasmic, whereas that of p62 and LDH5 was both cytoplasmic and nuclear. A median count of 0.90 "stone-like" structures per 200 × optical field (range 0-3.6) was highly associated with a high Gleason score. Similarly, a strong cytoplasmic LC3A, LC3B, and p62 expression, when extensive (present in>50% tumor cells per section), was significantly associated with LDH5 and a high Gleason score. In addition, extensive cytoplasmic p62 expression was related with LC3A and B reactivity and also with extraprostatic invasion. Extensive Beclin-1 expression was significantly linked with extraprostatic invasion and also with p62 and LDH5 expression. CONCLUSIONS: Immunohistochemical detection of autophagy proteins may potentially prove to be useful as prognostic markers and a tool for the stratification of patients in therapeutic trials targeting autophagy in prostate cancer.
Authors: Efthimios Sivridis; Ioannis M Koukourakis; Stella Arelaki; Kostantina Balaska; Antonios Karpouzis; Alexandra Giatromanolaki Journal: Head Neck Pathol Date: 2019-04-11
Authors: Aaron R Hansen; Ian F Tannock; Arnoud Templeton; Eric Chen; Andrew Evans; Jennifer Knox; Amy Prawira; Srikala S Sridhar; Susie Tan; Francisco Vera-Badillo; Lisa Wang; Bradly G Wouters; Anthony M Joshua Journal: Oncologist Date: 2019-04-05