High level of microtubule-associated protein light chain 3 predicts poor prognosis in resectable esophageal squamous cell carcinoma

Int J Clin Exp Pathol. 2014 Jun 15;7(7):4213-21. eCollection 2014.

Abstract

Microtubule-associated protein light chain 3 (LC3) is a key mediator bridging autophagy, apoptosis and differentiation. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the clinical significance of LC3 by immunohistochemistry in a group of patients with ESCC treated with surgical resection. Tissue microarray that included 253 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of LC3 expression was analyzed statistically. The association of LC3 expression with the ESCC survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. The results showed that the immunostaining of LC3 was distributed in cytoplasm and plasma-membrane. Significantly high LC3 expression was found in ESCC cells compared with that of normal esophageal epithelial cells. Patients with low expression of LC3 demonstrated higher overall survival compared with those with high expression of LC3 (mean of 71.1 months versus 55.5 months, P = 0.022). A similar result was observed for disease-free survival (mean of 68.7 months versus 51.8 months, P = 0.021). In subgroup analysis, LC3 expression could stratify pN0 patients with ESCC. Multivariate analysis showed that the level of LC3 expression was an independent prognostic factor in ESCC (RR = 1.407, P = 0.049). This paper shows high level of LC3 suggests poor prognosis for resectable ESCC patients.

Keywords: Esophageal cancer; LC3; immunohistochemistry; surgery.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology*
  • Disease-Free Survival
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / biosynthesis*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins