Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas

Abstract

Background: Lung carcinoma has a poor prognosis that is mainly predicted by the stage of the disease. Despite evaluation of various prognostic factors, the role of autophagy, a self-degradative process involved in the turnover of cytoplasmic material, remains unexplored in lung malignancy.

Methods: Autophagic activity was investigated in 115 patients with non-small cell lung carcinoma treated with surgery (64 squamous cell carcinomas, 24 adenocarcinomas of mixed subtype, 18 large cell carcinomas, 9 uncommon types). The median overall survival was 32 months (range, 2-102 months). We used the MAP1LC3A antibody and a standard immunohistochemical technique. Autophagic activity was correlated with clinical and pathologic parameters.

Results: Immunohistochemical examination revealed three patterns of autophagic activity: diffuse cytoplasmic, cytoplasmic perinuclear, and "stone-like" structures (SLSs), which are dense, rounded cytosolic structures typically enclosed within light-chain 3 (LC3) A-positive vacuoles. A high SLS count was associated with a reduction of the overall median survival from 88 to 15 months and constituted the strongest independent variable in multivariate analysis. Interestingly, a high presence of SLS defined significantly poor prognosis within stage I and II, whereas a similar trend was noted within stage III. The other two patterns of LC3A reactivity were not correlated with prognosis.

Conclusions: Exaggerated autophagy, as indicated by the intense presence of SLSs, is strongly correlated with a poor outcome in non-small cell lung carcinoma, suggesting possibly that autophagy functions as a survival tool in cancer cells.