Abstract
BackgroundWidespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.MethodsIn 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.ResultsThere 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.ConclusionCompared 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.
Highlights
Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS)
There was no difference in nuclear grade between the two groups but a necrotic focus was found at a significantly higher frequency in DCIS-Mi (85.7%) than in DCIS (51.9%) (P = 0.0017)
Relative expression of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki67: DCIS vs. DCIS-Mi There was no significant difference between DCIS and DCIS-Mi in expression levels of universal biological factors such as estrogen receptor (ER), progesterone receptor (PgR), and HER2
Summary
Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). In situations where there are multiple foci of microinvasion, the classification is based on the largest focus, rather than the sum of all the individual foci and if the size of the largest focus is less than 0.1 cm, the lesion will still be defined as T1mic [5] This ductal carcinoma in situ with microinvasion, known as DCISMi, is identified in 10–20% of cases thought to be DCIS, through the use of preoperative diagnostic imaging and cytology; it is considered to represent the interim stage in the progression from DCIS to IDC [6,7,8]. The survivin gene, shown to be expressed in proliferating cells such as fetal and various cancer cells, is known to be a member of the inhibitor of apoptosis protein (IAP) family, which promotes cell proliferation and inhibits apoptosis [18,19,20,21]
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