Oncotarget

Research Papers: Pathology:

Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas

Olivia Adams, Bastian Dislich, Sabina Berezowska, Anna M. Schläfli, Christian A. Seiler, Dino Kroell, Mario P. Tschan and Rupert Langer _

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Oncotarget. 2016; 7:39241-39255. https://doi.org/10.18632/oncotarget.9649

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Abstract

Olivia Adams1,2, Bastian Dislich1, Sabina Berezowska1, Anna M. Schläfli1, Christian A. Seiler3, Dino Kroell3, Mario P. Tschan1,2 and Rupert Langer1

1 Institute of Pathology, University of Bern, Bern, Switzerland

2 Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland

3 Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland

Correspondence to:

Rupert Langer, email:

Keywords: esophageal adenocarcinoma, autophagy, LC3B, p62, Pathology Section

Received: January 05, 2016 Accepted: May 13, 2016 Published: May 26, 2016

Abstract

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.


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