Differences in autophagy-related activity by molecular subtype in triple-negative breast cancer

Abstract

The aim of this study was to assess the expression of significant components of autophagy including beclin-1, light chain (LC) 3A, LC3B, and p62 in the molecular subtypes of triple-negative breast cancer (TNBC) and to evaluate the implications of the results. Tissues from 119 cases of TNBC were used for a tissue microarray. Expression of cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin7, E-cadherin, androgen receptor (AR), and gamma-glutamyltransferase 1 (GGT-1) was detected by immunohistochemical staining of the tissue microarrays. According to the results, the 119 cases of TNBC were subclassified into basal-like type (CK5/6-positive and/or EGFR-positive group), molecular apocrine type (AR-positive and/or GGT-1-positive group), claudin low type (claudin 3-, claudin 4-, or claudin 7-negative and/or E-cadherin-negative group), mixed type (having the features of more than two types), or null type (none of the above). Immunohistochemical staining for autophagy-related markers including beclin-1, LC3A, LC3B, and p62 was performed to evaluate the difference between clinicopathological parameters. TNBCs were categorized as basal-like type (36 patients, 30.3 %), molecular apocrine type (8 patients, 6.7 %), claudin low type (16 patients, 13.4 %), mixed type (37 patients, 31.1 %), and null type (22 patients, 18.5 %). Expression of nuclear p62 was higher in the molecular apocrine type and claudin low type than in other types of TNBC (p = 0.008). Expression of beclin-1 was higher in molecular apocrine type than in other TNBC types (p = 0.039). Expression of LC3A and LC3B showed no difference between the molecular subtypes. Multivariate Cox analysis revealed that the negative expression of p62 was associated with shorter disease-free survival [p = 0.012; odds ratio, 3.192; 95 % confidence interval (CI), 1.293-7.882] and shorter overall survival (p = 0.009; odds ratio, 3.895; 95 % CI, 1.409-10.771). Among the subtypes of TNBC, molecular apocrine breast cancer showed a higher expression of nuclear p62 and beclin-1 than others, which reflected higher autophagy activity.