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

Adams, Olivia Joan; Dislich, Bastian; Berezowska, Sabina Anna; Schläfli, Anna; Seiler, Christian A.; Kröll, Dino; Tschan, Mario; Langer, Rupert (2016). Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas. OncoTarget, 7(26), pp. 39241-39255. Impact Journals LLC 10.18632/oncotarget.9649

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Adams, Olivia Joan; Dislich, Bastian; Berezowska, Sabina Anna; Bill, Anna Magdalena; Seiler, Christian A.; Kröll, Dino; Tschan, Mario and Langer, Rupert

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

23 Dec 2016 09:56

Last Modified:

02 Feb 2018 10:03

Publisher DOI:

10.18632/oncotarget.9649

PubMed ID:

27250034

Uncontrolled Keywords:

LC3B; Pathology Section; autophagy; esophageal adenocarcinoma; p62

BORIS DOI:

10.7892/boris.92030

URI:

https://boris.unibe.ch/id/eprint/92030

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