Expression of autophagy-related markers beclin-1, light chain 3A, light chain 3B and p62 according to the molecular subtype of breast cancer

Histopathology. 2013 Jan;62(2):275-86. doi: 10.1111/his.12002. Epub 2012 Nov 8.

Abstract

Aims: To investigate the relationship between the expression of autophagy-related proteins, including beclin-1, light chain (LC) 3A, LC3B, and p62, and prognosis in invasive breast cancer.

Methods and results: We constructed tissue microarrays from the breast cancer cells of 489 patients, and classified molecular subtypes using surrogate immunohistochemical stains. The tumoral expression levels of LC3A and LC3B were highest in triple-negative breast cancer (TNBC) (P < 0.001), whereas these types of tumour had the lowest expression levels of these markers in the stroma (P = 0.005 and P < 0.001, respectively). Cytoplasmic beclin-1 expression was highest in TNBC, but nuclear expression was lowest (P < 0.001). p62 cytoplasmic and nuclear expression were highest in HER2-type tumours (P = 0.001 and P < 0.001, respectively). Tumoral LC3A and LC3B expression were associated with high histological grade (P < 0.001, and P < 0.028, respectively), but nuclear p62 expression was associated with lower histological grade (P = 0.004).

Conclusions: Autophagy-related markers are differentially expressed according to the molecular subtype of breast cancer. In particular, expression of LC3A, LC3B and beclin-1 was highest in TNBC tumour cells, whereas that of LC3A and LC3B in the tumour stroma was lowest in TNBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy
  • Beclin-1
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary*
  • DNA, Neoplasm / analysis
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Republic of Korea / epidemiology
  • Sequestosome-1 Protein
  • Survival Rate
  • Tissue Array Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • ERBB2 protein, human
  • Receptor, ErbB-2