Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer
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Anna M. Schläfli1, Olivia Adams1,2, José A. Galván1, Mathias Gugger1,3, Spasenija Savic4, Lukas Bubendorf4, Ralph A. Schmid5, Karl-Friedrich Becker6, Mario P. Tschan1,2, Rupert Langer1 and Sabina Berezowska1
1 Institute of Pathology, University of Bern, Bern, Switzerland
2 Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
3 Promed Laboratoire Médical, Marly, Switzerland
4 Institute of Pathology, Universty Hospital Basel, Basel, Switzerland
5 Division of General Thoracic Surgery, Inselspital University Hospital Bern, Bern, Switzerland
6 Institute of Pathology, Technische Universität München, München, Germany
Sabina Berezowska, email:
Keywords: autophagy, LC3, p62/SQSTM1, immunohistochemistry, non-small cell lung cancer
Received: April 09, 2016 Accepted: May 19, 2016 Published: May 26, 2016
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.
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