Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer

// Anna M. Schlafli 1 , Olivia Adams 1,2 , Jose A. Galvan 1 , Mathias Gugger 1,3 , Spasenija Savic 4 , Lukas Bubendorf 4 , Ralph A. Schmid 5 , Karl-Friedrich Becker 6 , Mario P. Tschan 1,2 , Rupert Langer 1 and Sabina Berezowska 1 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 Medical, 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 Universitat Munchen, Munchen, Germany Correspondence to: 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 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.