Expression of Autophagy-Related Proteins According to Androgen Receptor and HER-2 Status in Estrogen Receptor-Negative Breast Cancer

Abstract

Purpose: The purpose of this study was to investigate the expression of autophagy-related proteins in relation to androgen receptor (AR) status in estrogen receptor (ER)-negative breast cancers. Methods: We extracted 334 ER-negative breast cancer samples to construct tissue microarrays (TMAs), which were immunohistochemically stained for autophagy-related proteins (beclin-1, LC3A, LC3B, p62) and for AR and HER-2. Results: There were 127 AR-positive cases and 207 AR-negative cases, and 140 HER-2-positive cases and 194 HER-2 negative cases. The AR-negative group was associated with tumoral LC3A expression (P,0.001), while the AR-positive group was associated with tumoral BNIP3 expression (P,0.001). Tumoral LC3A was most highly expressed in the AR-negative and HER-2 negative group, while stromal LC3A showed the highest expression in the AR-negative and HER-2-positive group. Tumoral BNIP3 and stromal BNIP3 were highest in the AR-positive and HER-2-negative group. In the AR-positive and HER-2-negative group, stromal p62 positivity was an independent factor that was statistically significant in its association with shorter disease-free survival (DFS) (Hazard ratio: 10.21, 95 % CI: 1.130–92.31, P = 0.039). Shorter DFS was associated with tumoral LC3A positivity (Hazard ratio: 10.28, 95 % CI: 2.068–51.19, P = 0.004) in the AR-negative and HER-2-positive group. Conclusion: In ER-negative breast cancers, AR status was associated with expression of different types of autophagy-related proteins. Tumoral LC3A was most highly expressed in AR-negative breast cancers, while tumor BNIP3 was highest in AR