Mad1 protein is known to repress Myc target genes and antagonize Myc function. We underwent this study to investigate the clinical implication of Mad1 expression in human breast cancer.

We performed immunohistochemical assay for Mad1 protein together with Myc in human breast cancer, along with tissues from normal and benign diseases. The data from protein assay were merged with clinical and biologic parameters of the patients.

Of 66 patientswith invasive ductal cancer, Mad1 expression was detected in 22(33.3%). Intensity and area of Mad1 expression significantly decreased in DCIS and invasive cancers while high levels of Mad1 expression were persistent in benign breast lesions. Mad1 expression was significantly reduced in poorly differentiated tumors(p<0.00l). Expression of Mad1 was not associated with tumor size, lymph node status, and stage of the disease. We could not observe any correlation between S-phase and expression status of Myc or Mad1. Mad1 expression was closely linked to differentiation of the cancer cells and inversely correlated with Myc expression(p=0.042). In survival analysis, Mad1 possessed a prognostic significance to predict recurrence of the disease but not overall survival after CMF chemotherapy.

In human breast cancer cells, expression of Mad1 seems to be downregulated while expression of Myc is amplified. Altered expression of Mad I may play a role in malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast cancer.