title: Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas.
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.
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Adams
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Bastian
authors.initials: B
authors.lastname: Dislich
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berezowska
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Schläfli
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Seiler
authors.affiliation: Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland.
authors.forename: Dino
authors.initials: D
authors.lastname: Kröll
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Mario P
authors.initials: MP
authors.lastname: Tschan
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy; D014408:Biomarkers, Tumor / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000737:chemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins
keywords: LC3B; Pathology Section; autophagy; esophageal adenocarcinoma; p62