PubMed · 11462449
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T Ishii. 2001. [Breast].. https://pubmed.ncbi.nlm.nih.gov/11462449/
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To investigate changes in gene expression associated with ERBB2, expression profiling of immortalized human mammary luminal epithelial cells and variants expressing a moderate and high level of ERBB2 has been carried out using cDNA microarrays corresponding to approximately 6000 unique genes/ESTs. A total of 61 significantly up- or downregulated (2.0-fold) genes were identified and further validated by RT-PCR analysis as well as microarray comparisons with a spontaneously ERBB2- overexpressing breast cancer cell line and ERBB2-positive primary breast tumors. The expression and clinical relevance of proteins predicted to be associated with ERBB2 overexpression in breast cancers were analysed together with their clinical relevance by antibody screening using a tissue array. Differentially regulated genes include those involved in cell-matrix interactions including proline 4-hydroxylase (P4HA2), galectin 1 (LGALS1) and galectin 3 (LGALS3), fibronectin 1 (FN1) and p-cadherin (CDH3), and cell proliferation (CRIP1, IGFBP3) and transformation (S100P, S100A4). A number of genes associated with MYC signalling were also differentially expressed, including NDRG1, USF2 and the epithelial membrane proteins 1 and 3 (EMP1, EMP3). These data represent profiles of the transcriptional changes associated with ERBB2-related pathways in the breast, and identify novel and potentially useful targets for prognosis and therapy.
PURPOSE: To evaluate the effectiveness of noninvasive magnetic resonance (MR) imaging-guided focused ultrasonographic (US) ablation of breast carcinomas. MATERIALS AND METHODS: Before undergoing tumor resection, 12 patients with invasive breast carcinomas were treated with MR imaging-guided focused US ablation consisting of multiple sonications of targeted points that were monitored with temperature-sensitive MR imaging. The patients were treated with either one of two focused US systems. The effectiveness of the treatment was determined at histopathologic analysis of the resected mass that was performed to determine the volumes of necrosed and residual tumor. Complications resulting from the procedure were assessed by means of questionnaires, medical examinations, and MR image analysis. RESULTS: US ablation was well tolerated by the patients, and with the exception of minor skin burns in two patients, no complications occurred. Histopathologic analysis of resected tumor sections enabled quantification of the amount of necrosed and residual tumor and visualization of the surrounding hemorrhage. In three patients treated with one of the US systems, a mean of 46.7% of the tumor was within the targeted zone and a mean of 43.3% of the cancer tissue was necrosed. In nine patients treated with the other US system, a mean of 95.6% of the tumor was within the targeted zone and a mean of 88.3% of the cancer tissue was necrosed. Residual tumor was identified predominantly at the periphery of the tumor mass; this indicated the need to increase the total targeted area (ie, with an increased number of sonications). CONCLUSION: Thermal coagulation of small breast tumors by means of MR imaging-guided focused US appears to be a promising noninvasive ablation procedure.
Currently, the therapy for breast cancer is determined by immunohistochemical staining of the primary tumour for oestrogen receptor alpha (ERalpha). However, a proportion of ERalpha-positive patients fail to respond to tamoxifen and a proportion of ERalpha-negative patients show response. Here, we describe a novel procedure for the purification of malignant breast epithelial cells in an attempt to identify these patients at an early stage. Using this procedure, we are able to purify malignant cells to >90% purity as determined by immunohistochemical staining, cytology and fluorescent in situ hybridisation (FISH). While the malignant cells can be maintained in culture they do not proliferate in contrast to purified breast epithelial cells from reduction mammoplasties. Moreover, ERalpha and progesterone receptor (PR) expression is maintained in malignant cells, whereas normal epithelial cells rapidly lose ERalpha and PR. Functional studies were performed on the separated malignant cells in terms of their response to oestradiol and tamoxifen. Four out of the seven ERalpha-positive tumours showed a significant reduction in cell numbers after tamoxifen treatment compared to oestradiol, ERalpha negative tumours failed to show a response. We conclude that (a) it is possible to purify and maintain breast cancer cells for a sufficient period to permit functional studies and (b) ERalpha is retained in culture facilitating the use of these cells in studies of the mechanism of endocrine response and resistance in vitro.