We propose to investigate the angiogenesis status in stage I and II invasive ductal carcinoma (IDC) of the breast by immunohistochemistry (IHC) and magnetic resonance imaging (MRI). Angiogenesis is the formation of new blood vessels within tumors, which is essential for the growth and spread of cancer. Because angiogenesis is thought to be a very early event in cancer pathogenesis, a better characterization of its status may aid in appropriate management of disease by administering the most appropriate treatment protocol. Supporting evidence has indicated that the angiogenesis is associated with the aggressiveness of the primary cancer. The long-term goal is to predict the risk of future relapse and metastasis. The angiogenic molecular markers, including mutant p53, thrombospondin-1 (TSP-1), CD31 (vascular marker) and CD-105 (neovascular marker) vessel density, and VEGF (Vascular Endothelial Growth Factor), can be quantitatively measured with IHC analysis. These markers have been shown to be good prognostic indicators. However, since the study is performed from a thin slide of a cancer, the inadequate sampling may result in values that are not representative of the whole tumor. New vessel formation results in a higher vascularity and a leakier structure, which can be detected by dynamic contrast enhanced MRI. This technique has been shown as a non-invasive means to measure the vascular characteristics in tumors. The enhancement kinetics can be analyzed with pharmacokinetic models to derive the vascular volume and vascular permeability parameters. The former is related to the blood flow supplied to the tumor, and the latter is related to the leakage status (or, maturity) of vessels, which are two important properties of a tumor. Therefore, MRI can be used to measure the vascularity from a thorough sampling of the entire tumor, thus may provide supplementary information to the IHC markers for the assessment of angiogenesis more accurately. In this study we will apply IHC and dynamic MRI to characterize the angiogenic status of early breast cancer (invasive ductal carcinoma, stage I and II). The patients with suspected malignant breast lesions will be first studied with MRI. Then surgical biopsy will be performed, and the specimen will be sent for pathological examination and IHC. The patients will be followed closely for lymphatic involvement and developments of recurrence and metastasis. After the studies are completed, we will determine the predictive value of MRI, IHC, and a combination of MRI + IHC for their association with the initial lymph node involvement. If a strong correlation can be established, the painful procedure of lymph node dissection may be aborted. The successful outcome of the current proposal should enhance the accuracy of the prognostic factors and reduce the treatment-associated morbidity while also reducing the long-term mortality by selecting the """"""""correct treatment.""""""""
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