title: Autophagy proteins in prostate cancer: relation with anaerobic metabolism and Gleason score.
abstract: OBJECTIVE
  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.affiliation: Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece. Electronic address: agiatrom@med.duth.gr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
authors.affiliation: Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.affiliation: Division of Pathology Integrated Medical Professionals, New York, NY.
authors.forename: Savvas
authors.initials: S
authors.lastname: Mendrinos
authors.affiliation: Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Anastasios V
authors.initials: AV
authors.lastname: Koutsopoulos
authors.affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001343:Autophagy; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; D007527:Isoenzymes; C477012:MAP1LC3A protein, human; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: Autophagy; LC3A; LC3B; LDH5; Prostate cancer; p62