Garcia, S. et al. c-Met overexpression in inflammatory breast carcinomas: automated quantification on tissue microarrays. Br. J. Cancer 96, 329-335

Department of Pathology, Centre Hospitalo-Universitaire Nord, Marseille, France.
British Journal of Cancer (Impact Factor: 4.84). 02/2007; 96(2):329-35. DOI: 10.1038/sj.bjc.6603569
Source: PubMed


Inflammatory breast carcinoma (IBC) is a rare but aggressive tumour associated with poor outcome owing to early metastases. Increased expression of c-Met protein correlates with reduced survival and high metastatic risk in human cancers including breast carcinomas and is targetable by specific drugs, that could potentially improve the prognosis. In the present study, we compared c-Met expression in IBC (n=41) and non-IBC (n=480) immunohistochemically (Ventana Benchmark autostainer) in two tissue microarrays (TMA) along with PI3K and E-cadherin. The results were quantified through an automated image analysis device (SAMBA Technologies). We observed that (i) c-Met was significantly overexpressed in IBC as compared with non-IBC (P<0.001), (ii) PI3K was overexpressed (P<0.001) in IBC, suggesting that the overexpressed c-Met is functionally active at least through the PI3K signal transduction pathway; and (iii) E-cadherin was paradoxically also overexpressed in IBC. We concluded that overexpressed c-Met in IBC constitutes a potential target for specific therapy for the management of patients with poor-outcome tumours such as IBC. Automated image analysis of TMA proved to be a valuable tool for high-throughput immunohistochemical quantification of the expression of intratumorous protein markers.

Download full-text


Available from: jean-philippe Dales
  • Source
    • "Additionally, the overexpression of c-Met has been shown to contribute to the development and progression of different human malignancies including lung, prostate, colorectal, gastric, and breast cancer [29]. Recently, it was reported that c-Met protein is overexpressed in inflammatory breast cancer compared to non-inflammatory breast cancer, and that an imbalance of c-Met protein expression between tumor and surrounding normal tissue is associated with an aggressive DCIS phenotype [30,31]. In the present study, c-Met protein was easily detectable and uniformly distributed throughout the normal breast. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes. Fresh normal breast tissue was collected from reduction mammoplasty patients and immediately placed into embedding medium and frozen on dry ice. Tissue sections were subjected to laser capture microscopy to isolate the interlobular from the intralobular fibroblasts. RNA was prepared and subjected to microarray analysis using the Affymetrix Human Genome U133 GeneChip. Data was analyzed using the Affy and Limma packages available from Bioconductor. Findings from the microarray analysis were validated by RT-PCR and immunohistochemistry. No statistically significant difference was detected between the gene expression profiles of the interlobular and intralobular fibroblasts by microarray analysis and RT-PCR. However, for some of the genes tested, the protein expression patterns between the two subtypes of fibroblasts were significantly different. This study is the first to report the gene expression profiles of the two distinct fibroblast populations within the human mammary gland. While there was no significant difference in the gene expression profiles between the groups, there was an obvious difference in the expression pattern of several proteins tested. This report also highlights the importance of studying gene regulation at both the transcriptional and post-translational level.
    Full-text · Article · Feb 2008 · BMC Cell Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The automated train dispatching system (ATDS) is a computerized fault tolerant train schedule tracking and status information system. It consists of thirty-eight DEC PC workstations interconnected by modems, thick and thin wire Ethernet and fiber optic cable to a central VAXft computer acting as a database server. Three DECserver 700s provide forty-eight ports to drive nine end of line printers and three hundred “Transit Information Display Sign” (TIDS) Displays. The ATDS will be used by dispatchers and tower operators to monitor and administer the movement of trains in their territory by providing an accurate, real time status of train location. The inner workings of the traditional paper intensive system used to “run the railroad” are examined. The problems common to this system are identified and their impact assessed. The functionality of the new system is described. The streamlined operations under the electronic system are explained together with a discussion of the problems encountered when implementing the new design. The impacts on not only railroad operations but other departments with respect to the introduction of new technology, new technology/work interface and organization structure are explored. Integration of the design into the overall modernization plans are explored and finally, the lessons learned in implementation of this project are listed
    No preview · Conference Paper · Apr 1994
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory breast cancer (IBC) is a rare, but aggressive form of breast cancer. Despite the progress related to the introduction of primary combination chemotherapy (CT) to the multimodality treatment regimen, the prognosis of IBC remains poor with long-term survival inferior to 50%. Until recently, IBC remained understudied at the molecular level. In the past 10 years, advances have been made in the molecular characterization of the disease. Recently, the use of experimental models and new high-throughput molecular profiling technologies have led to the identification of genes or pathways potentially involved in disease development, which might represent new clinically relevant targets. The aim of this review is to present and discuss what is known about the biology of this particularly aggressive form of breast cancer and to discuss how this knowledge could improve its management.
    No preview · Article · Mar 2008 · Seminars in Oncology
Show more