1Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea. 2Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea.
ABSTRACT
PURPOSE: Madl protein is known to directly repress Myc target genes and antagonize Myc function. Consequently, Madl is considered to function as a tumor suppressor. We undertook this study to investigate the regulatory effect of Madl on cancer progression in human breast cancer.
MATERIALS AND METHODS: We performed immunohistochemical assay for Madl protein together with Myc in human breast cancer as well as tissues from normal and benign diseases.
The protein assay data were evaluated together with clinical and biologic parameters of the patients.
RESULTS: Of 66 patients with invasive ductal cancer, Madl expression was detected in 22 patients (33.3%) with breast cancer. Intensity and area of Madl expression significantly decreased in DCIS and invasive cancers, while high levels of Madl expression were persistent in benign breast lesions.
Madl expression was significantly reduced in poorly differentiated tumors (p=0.0002). Expression of Madl was not associated with size of the tumors, lymph node status, and stage of the disease. We could not observe any correlation between S-phase and expression status of Myc or Madl. Madl expression was closely linked to differentiation of the cancer cells and inversely correlated with Myc expression (p=0.042). In survival analysis, Madl possessed a prognostic significance in predicting recurrence of the disease but not overall survival after CMF chemotherapy.
CONCLUSIONS: In human breast cancer cells, expression of Madl seems to be downregulated while expression of Myc is amplified. Altered expression of Mad1 may play a role in malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast cancer.
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