Expression of DNA methylation-related proteins in breast phyllodes tumor

Abstract

The purpose of this study is to research the expression of DNA methylation-related proteins in phyllodes tumors of the breast and to study the implication on patient outcomes. We generated tissue microarrays (TMAs) of 196 phyllodes tumors (PT) and performed immunohistochemical staining for 5-meC and the DNA methylationrelated proteins DNMT1 and ISL-1. The staining results were analyzed and compared with clinicopathologic parameters. A total of 196 cases were included in this study, of which 153 were benign, 27 were borderline, and 16 were malignant. The levels of DNMT1, 5 meC, and ISL-1 in the stromal component of tumors increased with increasing grade (P<0.001). Especially, high stromal positivity of DNMT1 and ISL-1 were associated with increased distant metastasis (P=0.001, and P=0.013, respectively). Univariate analysis for factors associated with decreased disease free survival and overall survival identified DNMT1 high positivity (P=0.002 and P<0.001, respectively) and stromal ISL-1 high positivity (P<0.001 and P<0.001, respectively). Among borderline phyllodes tumors, stromal DNMT1 high positivity was associated with decreased OS (P=0.015). In conclusion, DNA methylation and expression of methylation-related proteins in the stromal component increased with increasing histologic grade in phyllodes tumors. In addition, overexpression stromal expression of DNMT1 and ISL-1 was associated with poor prognosis.