Research Papers:

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

Anna M. Schläfli, Olivia Adams, José A. Galván, Mathias Gugger, Spasenija Savic, Lukas Bubendorf, Ralph A. Schmid, Karl-Friedrich Becker, Mario P. Tschan, Rupert Langer and Sabina Berezowska _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:39544-39555. https://doi.org/10.18632/oncotarget.9647

Metrics: PDF 3201 views  |   HTML 4133 views  |   ?  


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

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


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 9647