LC3A‐Positive “Stone‐Like” Structures Predict an Adverse Prognosis of Gastric Cancer

Abstract

Microtubule-associated protein light chain 3 (LC3A) is a reliable marker of autophagy that displays three distinct patterns of immunohistochemical staining in solid tumors: diffuse cytoplasmic staining, juxtanuclear staining, and staining of "stone-like" structures. These three patterns have a different prognostic significance in many solid tumors, but little is known about their influence in gastric cancer (GC). This study was a retrospective analysis of 188 GC patients from stages I to IV. The pattern of LC3A expression was examined in tumor and nontumor tissues by immunohistochemistry. Then, the association between the pattern of LC3A expression in GC and the prognosis was investigated by Kaplan-Meier analysis and the Cox proportional hazards model. Two distinct patterns of LC3A immunostaining (diffuse cytoplasmic expression and "stone-like" structures) were observed in GC tissues. LC3A-positive "stone-like" structures were found only in the tumors, and the number of such structures was correlated with both the tumor type and tumor stage. In addition, a high number of LC3A-positive "stone-like" structures was closely associated with an increased risk of recurrence after radical resection of stages I-III cancer (P < 0.001; HR = 0.205) and was associated with a lower overall survival rate for stage IV cancer (P < 0.001; HR = 0.364). Taken together, our data demonstrate that LC3A-positive "stone-like" structures can be used as an independent biomarker for an adverse prognosis of GC, suggesting that "stone-like" structures are correlated with the malignancy of this disease.