Abstract P2-05-03: Mouse double minute 2 nuclear expression as a prognostic marker in patients with breast cancer

BACKGROUND: Mouse double minute 2 (Mdm2) is a negative regulator of tumor suppressor, p53, thus Mdm2 expression may play a role in cancer development and prognosis, however, the definite role of Mdm2 in breast cancer is unclear. The aim of the study is to evaluate the correlation between Mdm2 expression and prognosis of breast cancer. METHODS: Mdm2 expression was determined from immunohistochemistry of tissue microarrays of 865 patients with breast cancer who underwent surgery. Clinicopathologic characteristics and survival data were analyzed using a univariate and multivariate analysis. Mdm2 expression was categorized into 3 groups: negative; no Mdm2 expression in nucleus and cytoplasm, cytoplasm-positive; cytoplasmic expression of Mdm2, nucleus-positive; nuclear with or without cytoplastimc expression of Mdm2. RESULTS: Negative, cytoplasm-positive, and nucleus-positive groups were observed in 59.2%, 10.9%, and 29.9% of patients, respectively. Nucleus-positive group was associated with young age, high grade, negativity of estrogen and progesterone receptor, HER2 positivity, and high Ki-67 index. With median 86.0 follow-up months, nucleus-positive group showed poorer disease-free survival and overall survival than negative and cytoplasm-positive groups. In multivariate analysis, cytoplsmic expression of Mdm2 was not significantly associated with survival, whereas nuclear expression of Mdm2 was related to poor prognosis. (HR, 1.44; 95% CI, 1.041–1.993 for DFS; HR, 1.546; 95% CI, 1.060–2.255 for OS) CONCLUSIONS: Nuclear expression of Mdm2 was an independent prognostic factor in patients with breast cancer. Patterns of Mdm2 expression in tumor cell should be rendered in the evaluation of Mdm2 in breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-03.