Expression of autophagy-related proteins in metastatic breast cancer of different site

Abstract

The aim of this study was to evaluate the expression of autophagy-related proteins and their clinical implications in primary and metastatic breast cancer. Immunohistochemical staining of autophagy-related proteins (beclin-1, LC3A, LC3B) in 162 metastatic breast cancers (bone metastasis = 47, brain metastasis = 39, liver metastasis = 24, and lung metastasis = 52) was performed using tissue microarray (TMA). The expression of autophagy-related proteins in tumor cells varied according to metastatic site. Tumoral LC3A expression was high in brain and lung metastasis (P<0.001), stromal LC3A in bone metastasis (P<0.001), and stromal LC3B in liver metastasis (P = 0.017), respectively. In univariate analysis, beclin-1 positivity (P = 0.002) was associated with shorter overall survival (OS). In analysis by metastatic site, beclin-1 positivity (P = 0.002) and activated autophagy status (P = 0.009) in bone metastasis as well as beclin-1 positivity (P = 0.016) and tumoral LC3A positivity (P = 0.038) in lung metastasis were related to shorter OS. In conclusion, the expression of autophagy-related proteins varied according to the site of metastasis and was correlated with prognosis.