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Clinical implication of altered expression of Mad1 protein in human breast carcinoma
Author(s) -
Han Sehwan,
Park Kyeongmee,
Kim HongYong,
Lee MyungSoo,
Kim HongJoo,
Kim YoungDuck,
Yuh Young Jin,
Kim Sung Rok,
Suh Hyun Suk
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000401)88:7<1623::aid-cncr17>3.0.co;2-w
Subject(s) - medicine , breast cancer , cancer research , immunohistochemistry , carcinoma , cancer , breast carcinoma , oncology , lymph node , pathology
BACKGROUND Mad1 protein is known to repress Myc target genes and antagonize Myc function. The authors undertook this study to investigate the clinical implication of Mad1 expression in human breast carcinoma. METHODS The authors performed immunohistochemical assays for Mad1 and Myc proteins in human breast carcinoma, along with tissues from normal breast and benign diseases. The data from protein assays were analyzed in terms of the clinical and biologic characteristics of the patients. RESULTS Of 66 patients with invasive ductal carcinoma, Mad1 expression was detected in 22 (33.3%). Intensity and area of Mad1 expression significantly decreased in DCIS and invasive cancers, whereas high levels of Mad1 expression were persistent in benign breast lesions. Mad1 expression was significantly reduced in poorly differentiated tumors ( P < 0.001). Expression of Mad1 was not associated with tumor size, lymph node status, or stage of disease. The authors did 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 was a significant factor in predicting recurrence of the disease, but not overall survival after CMF chemotherapy. CONCLUSIONS In human breast carcinoma cells, expression of Mad1 seems to be down‐regulated, whereas expression of Myc is amplified. Altered expression of Mad1 may play a role in the malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast carcinoma. Cancer 2000;88:1623–32. © 2000 American Cancer Society.