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Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas.

  • Adams O Institute of Pathology, University of Bern, Bern, Switzerland.
  • Dislich B Institute of Pathology, University of Bern, Bern, Switzerland.
  • Berezowska S Institute of Pathology, University of Bern, Bern, Switzerland.
  • Schläfli AM Institute of Pathology, University of Bern, Bern, Switzerland.
  • Seiler CA Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland.
  • Kröll D Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland.
  • Tschan MP Institute of Pathology, University of Bern, Bern, Switzerland.
  • Langer R Institute of Pathology, University of Bern, Bern, Switzerland.
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  • 2016-06-03
Published in:
  • Oncotarget. - 2016
LC3B
Pathology Section
autophagy
esophageal adenocarcinoma
p62
Adenocarcinoma
Adult
Aged
Aged, 80 and over
Autophagy
Biomarkers, Tumor
Esophageal Neoplasms
Female
Humans
Lysosomes
Male
Microtubule-Associated Proteins
Middle Aged
Prognosis
RNA-Binding Proteins
Treatment Outcome
English Esophageal adenocarcinomas (EAC) are aggressive tumors with considerable rates of chemoresistance. Autophagy is a lysosome-dependent degradation process, characterized by the formation of vesicles called autophagosomes, and has been implicated in cancer. Protein light chain 3 B (LC3B) and p62 are associated with autophagosomal membranes and degraded. We aimed to assess the impact of basal autophagy on EAC. In EAC cell lines, an increase in LC3B and p62 was observed with increasing concentrations of the autophagy inhibitor chloroquine, which indicates functional basal autophagy. LC3B and p62 immunohistochemistry was performed on primary resected EAC. High LC3B and p62 expression was associated with earlier tumor stages (p < 0.05). High nuclear and cytoplasmic p62 staining were associated with a better prognosis (p = 0.006; p = 0.028). Various combinations of p62 expression with or without LC3B expression identified different prognostic groups. Tumors with low total p62 (p = 0.007) or low LC3B/low p62 expression had the worst outcome (p = 0.007; p = 0.005). A combination score of dot-like/cytoplasmic p62 and nuclear p62 staining was an independent prognostic parameter (p = 0.033; HR = 0.6). This study highlights the potential significance of basal autophagy in EAC biology. Tumors with low LC3B and p62 expression show the most aggressive behavior and may be candidates for autophagy regulating therapeutics.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/28667
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