title: Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas.
abstract: BACKGROUND
  Lung carcinoma has a poor prognosis that is mainly predicted by the stage of the disease. Despite evaluation of various prognostic factors, the role of autophagy, a self-degradative process involved in the turnover of cytoplasmic material, remains unexplored in lung malignancy.
  
  
  METHODS
  Autophagic activity was investigated in 115 patients with non-small cell lung carcinoma treated with surgery (64 squamous cell carcinomas, 24 adenocarcinomas of mixed subtype, 18 large cell carcinomas, 9 uncommon types). The median overall survival was 32 months (range, 2-102 months). We used the MAP1LC3A antibody and a standard immunohistochemical technique. Autophagic activity was correlated with clinical and pathologic parameters.
  
  
  RESULTS
  Immunohistochemical examination revealed three patterns of autophagic activity: diffuse cytoplasmic, cytoplasmic perinuclear, and "stone-like" structures (SLSs), which are dense, rounded cytosolic structures typically enclosed within light-chain 3 (LC3) A-positive vacuoles. A high SLS count was associated with a reduction of the overall median survival from 88 to 15 months and constituted the strongest independent variable in multivariate analysis. Interestingly, a high presence of SLS defined significantly poor prognosis within stage I and II, whereas a similar trend was noted within stage III. The other two patterns of LC3A reactivity were not correlated with prognosis.
  
  
  CONCLUSIONS
  Exaggerated autophagy, as indicated by the intense presence of SLSs, is strongly correlated with a poor outcome in non-small cell lung carcinoma, suggesting possibly that autophagy functions as a survival tool in cancer cells.
authors.affiliation: Departments of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karpathiou
authors.affiliation: Departments of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.affiliation: Radiotherapy/Oncology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.affiliation: Cardiac/Thoracic Surgery, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mikroulis
authors.affiliation: Pneumonology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
authors.affiliation: Pneumonology, Democritus University of Thrace Medical School, Alexandroupolis, Greece.
authors.forename: Marios E
authors.initials: ME
authors.lastname: Froudarakis
authors.affiliation: Departments of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece. Electronic address: agiatrom@med.duth.gr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate / Q000639:trends
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins