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Background  We assessed the expression of methylation-related proteins 5-meC, DNMT1, and ISL-1 in breast cancer and evaluated their relationship to clinicopathological factors.    Methods  Immunohistochemical staining for ER, PR, HER-2, Ki-67, 5-meC, DNMT1, and ISL-1 were performed on 348 breast cancer samples in tissue microarray. Samples were subgrouped into luminal A, luminal B, HER-2, or triple-negative breast cancer (TNBC) according to immunohistochemical staining for ER, PR, HER-2, and Ki-67. The tumor stroma was histologically subtyped into desmoplastic, sclerotic, normal-like, or inflammatory type.    Results  Tumor expression of DNMT1 differed by molecular subtype: it was higher in TNBC and lower in luminal A (p < 0.001) samples. DNMT1 expression was also related to higher histologic grade, ER negativity, PR negativity, and higher Ki-67 LI (p < 0.001). In western blot, protein expressions of DNMT1 and ISL-1 were higher in TNBC and relatively lower in the remaining subtypes. High tumor expression of DNMT1 was associated with shorter OS in univariate analysis (p = 0.041). DNMT1 and 5-meC were differentially expressed by stromal phenotype: 5-meC was higher in normal-like type and lower in sclerotic type (p = 0.049); DNMT1 was higher in inflammatory and lower in sclerotic type (p < 0.001).    Conclusions  Tumor expression of DNMT1 in breast cancer differed by molecular subtype and stromal histological type. DNMT1 was highly expressed in TNBC and in breast cancer with inflammatory stromal type.

Differential expression of the epigenetic methylation-related protein DNMT1 by breast cancer molecular subtype and stromal histology