title: [High-throughput quantification of tissue microarrays: identification of candidate target proteins in inflammatory breast cancer].
abstract: Inflammatory breast carcinoma (IBC) is a rare but very aggressive tumour phenotype. Increased c-Met protein expression correlates with reduced survival and a higher metastatic risk in many human malignancies, including breast cancer Several studies have shown that c-Met protein is targetable by specific drugs. Here we compared c-Met expression in IBC (n = 41) and non IBC (n = 480). Two microarrays of IBC and non IBC tissues were constructed and standardized. C-Met, P13K and E-cadherin were immunodetected (Ven-tana Benchmark Autostainer) on serial sections. The results were quantified with an automated image analysis device (SAMBA Technologies) by immunoprecipitate densitometry of each core section (0.6 microns thick). We found that (i) c-Met is significantly overexpressed in IBC compared to non IBC (p < 0. 001), (ii) P13K is also overexpressed (p < 0.001) in IBC, suggesting that overexpressed c-Met is functionally active, at least through the PI3K signal transduction pathway ; and (iii) E-cadherin is paradoxically overexpressed in IBC. We conclude that c-Met may constitute a target for specific therapy in patients with poor-prognosis malignancies like IBC Automated image analysis of TMA is a valuable tool for high-throughput quantification of the immunohistochemical expression of the tumor proteome.
authors.affiliation: Service de Pathologie (Anatomie et Cytologie Pathologiques) CHU Nord, chemin des Bour-reley, 13915 Marseille.
authors.forename: Colette
authors.initials: C
authors.lastname: Taranger-Charpin
authors.forename: Lucile
authors.initials: L
authors.lastname: Andrac-Meyer
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Dales
authors.forename: Séverine
authors.initials: S
authors.lastname: Carpentier-Meunier
authors.forename: Claudine
authors.initials: C
authors.lastname: Andonian
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Lavaut
authors.forename: Claude
authors.initials: C
authors.lastname: Allasia
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonnier
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D001706:Biopsy; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D003720:Densitometry; D005260:Female; D051417:Focal Adhesion Kinase 1; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D015820:Cadherins; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human