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

<p>Abstract</p> <p>Background</p> <p>Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma <it>in situ </it>(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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Expression of gelatinase (MMP-2 and MMP-9) and cyclooxygenase-2 (COX-2) in endometrial carcinoma

Objective: Matrix metalloproteinases (MMPs) are key players in the degradation of extracellular matrix and basement membranes, and are thus important in tumor invasion. Gelatinases (MMP-2 and MMP-9) in particular are prognostic factors in many solid tumors. In this study the immunohistochemical expression of both COX-2 and matrix metalloproteinases has been shown for the first time in endometrium carcinoma. Methods: Forty-two endometrial carcinoma tissues were immunostained for MMP2 antibody (1:100, Rabbit polyclonal), MMP9 antibody (]:100, Rabbit polyclonal) and CoX2 antibody (1: 100, Epitope specific rabbit antibody). Results: 90.5% of the cases were positive for MMP-2 and MMP-9, and 83.3% of the cases were positive for COX-2. A statistically significant association was found between COX-2 overexpression and FIGO stage (p = 0.001). A positive correlation was also found with histological grade (p = 0.006), myometrial invasion (p = 0.033), vascular invasion (p = 0.017), and lymphatic invasion (p = 0.007). A positive correlation was found between MMP-2 overexpression and vascular and lymphatic invasion (p 0.030 and p = 0.003, respectively). MMP-9 overexpression was also found to be correlated with vascular and lymphatic invasion (p 0.001 and p = 0.012, respectively). Furthermore, there was a statistically significant correlation between MMP-2 and MMP-9 overexpression (p = 0.0001). Conclusion: The results showed that COX-2, MMP-2 and MMP-9 were expressed in a high percentage of primary endometrial carcinomas and their expressions may be associated closely with parameters of tumor aggressiveness