Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion

In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.Ductal carcinoma in situ (DCIS) is thought to be a precursor of invasive ductal carcinoma (IDC) and is defined as a lesion in which cancer cells do not grow beyond the basal membrane of the mammary duct [1]. Since the introduction of mammography in breast cancer screening, increasing numbers of DCIS are now being identified [2]. About 10 years ago, DCIS accounted for only 1–5% of all newly diagnosed cases of breast cancer, whereas the frequency has increased recently to 15–20% [3,4]. According to the criteria of the American Joint Committee on Cancer (AJCC), IDC with a microscopic focus of invasion less than or equal to 0.1 cm in the longest dimension, is defined as T1mic [5]. In