title: Expression of DNA methylation-related proteins in metastatic breast cancer.
abstract: 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.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Cha
authors.forename: W H
authors.initials: WH
authors.lastname: Jung
authors.forename: J S
authors.initials: JS
authors.lastname: Koo
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary*; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000378:metabolism*; D045647:DNA Glycosylases / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D011980:Receptors, Progesterone
chemical_list: D014408:Biomarkers, Tumor; D011980:Receptors, Progesterone; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619380:DNMT1 protein, human; C093335:5-methylcytosine-DNA glycosylase; D045647:DNA Glycosylases
keywords: 5-meC metastasis.; DNA methylation; DNMT1; breast cancer