Autophagy is an evolutionarily conserved process that involves lysosomal degradations of cellular organelles. Microtubule-associated protein I light chain 3A (LC3A), an autophagic gene, is differentially expressed in human cancers. However, the relationship between LOA expression and hepatocellular carcinoma (HCC) has not been investigated. Tissue microarray-based immunohistochemistry was used to examine the expression patterns of LC3A in HCC. The resulting data were analyzed using receiver operating characteristic curves, Spearman's rank correlation, Kaplan Meier plots and Cox proportional hazards regression modeling. Two distinct patterns of LC3A expression were observed in HCC: "stone-like" structuring and diffuse cytoplasmic expression. High levels of LC3A expression were more frequently observed in HCC tissues compared to the adjacent non-tumorous tissue. Correlation analyses indicated that high expression of the "stone-like" LC3A was correlated with greater levels of serum AFP, poorer tumor differentiation and the presence of vascular invasion. Kaplan Meier survival analysis showed a significant association between high expression of the "stone-like" LC3A and unfavorable prognosis (P < 0.001). Importantly, multivariate analysis (P < 0.05) identified the "stone-like" expression of LC3A in HCC as an independent prognostic factor. Collectively, our data provide compelling evidence that "stone-like" expression of LC3A plays an important role in HCC progression and may act as a biomarker of prognosis for patients with HCC. (C) 2013 Elsevier Inc. All rights reserved.