We aimed to investigate the expression of methylation-related proteins (5-meC and DNMT1) in the metastatic breast cancers of variable sites and its association with clinicopathologic factors. A total of 126 metastatic breast cancers (31 bone metastases, 36 brain metastases, 11 liver metastases, 48 lung metastases) were made into tissue microarray and immunohistochemical staining of ER, PR, HER-2, Ki-67, 5-meC, and DNMT1 were performed. Molecular classification was made on the basis of immunohistochemical staining result of ER, PR, HER-2, Ki-67; luminal A, luminal B, HER-2, triple negative breast cancer (TNBC). Methylation-related proteins were differentially expressed based on the metastatic sites. Tumoral and stromal 5-meC showed the lowest expression in the bone metastasis (P < 0.001), tumoral DNMT1 showed the least expression in bone metastasis and the highest expression in the brain metastasis (P < 0.001). Expression of DNMT1 was correlated with ER negativity (P = 0.004), PR negativity (P = 0.011), HER-2 positivity (P = 0.016), higher Ki-67 labeling indices (P = 0.016), and non-luminal A type (P = 0.017). DNMT1 positivity was associated with shorter overall survival in bone metastasis (P = 0.017) and lung metastasis (P = 0.028) by univariate analysis. In conclusion, methylation-related proteins differentially expressed according to the metastatic sites in metastatic breast cancer. Tumoral and stromal 5-meC showed the lowest expression in the bone metastasis. Tumoral DNMT1 expression was low in bone metastasis and highest in brain metastasis.
Bibliographical noteFunding Information:
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1420080). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1A1A1A05001209).
© 2017, Cancer Research Institute Slovak Acad. of Sciences. All rights reserved.
All Science Journal Classification (ASJC) codes
- Cancer Research