title: Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer.
abstract: Autophagy is a cellular degrading process that promotes tumor cell survival or cell death in cancer, depending on the progress of oncogenesis. Protein light chain 3 (LC3) and p62/SQSTM1 (p62) are associated with autophagosomal membranes that engulf cytoplasmic content for subsequent degradation. We studied LC3 and p62 expression using immunohistochemistry in a large cohort of 466 stage I/II non-small cell lung cancer (NSCLC) using a tissue microarray. We evaluated dot-like cytoplasmic expression of LC3 and dot-like, cytoplasmic and nuclear staining for p62 in relation to clinico-pathological parameters.LC3 expression correlated with all p62 patterns, as those correlated among each other (p < 0.001 each). There was no correlation with stage, age or gender. A combination of high LC3/high p62 dot-like staining (suggesting impaired autophagy) showed a trend for better outcome (p = 0.11). Interestingly, a combined low cytoplasmic/low nuclear p62 expression regardless of dot-like staining was an independent prognostic factor for longer survival (p = 0.006; HR=1.96), in addition to tumor stage (p = 0.004; HR=1.4).The autophagy markers LC3 and p62 are differentially expressed in NSCLC, pointing towards a biologically significant role. High LC3 levels seem to be linked to lower tumor aggressiveness, while high general p62 expression was significantly associated with aggressive tumor behavior.
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Schläfli
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: José A
authors.initials: JA
authors.lastname: Galván
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.|Promed Laboratoire Médical, Marly, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.affiliation: Institute of Pathology, Universty Hospital Basel, Basel, Switzerland.
authors.forename: Spasenija
authors.initials: S
authors.lastname: Savic
authors.affiliation: Institute of Pathology, Universty Hospital Basel, Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.affiliation: Division of General Thoracic Surgery, Inselspital University Hospital Bern, Bern, Switzerland.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Schmid
authors.affiliation: Institute of Pathology, Technische Universität München, München, Germany.
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Becker
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
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berezowska
mesh_terms: D000368:Aged; D001343:Autophagy; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins
keywords: LC3; autophagy; immunohistochemistry; non-small cell lung cancer; p62/SQSTM1