title: Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis.
abstract: c-Met is responsible for cell motility and tumour spreading. c-Met expression and signal transducers reflecting c-Met functionality were investigated in breast carcinomas, in correlation with patient outcome and tumour vasculature. Tissue microarrays of 930 breast carcinomas were constructed, categorised according to patients' follow-up (4- to 10-year follow-up; median, 6.5 years). Standardised immunocytochemical procedures were performed using anti-c-Met, -PI3K, -FAK, -JAK, and -CD146, -FYN and an automated autostainer (Ventana). High-throughput densitometry measuring the extent of immunoprecipitates was assessed by image analysis (SAMBA). c-Met overexpression correlated with poor survival along with PI3K and FAK reflecting c-Met functionality and CD146 and FYN expression in endothelial cells. Automated quantification of immunocytochemical precipitates using image analysis was shown to provide an objective means of measuring cellular proteins that are potentially relevant for current practice in pathological diagnosis and for specific therapy combining inhibitors of both c-Met and downstream transducer pathways, and of tumour angiogenesis.
authors.affiliation: Department of Pathology, Centre Hospitalo-Universitaire, Hôpital Nord, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Garcia
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Dales
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Séverine
authors.initials: S
authors.lastname: Carpentier-Meunier
authors.forename: Lucile
authors.initials: L
authors.lastname: Andrac-Meyer
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
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
authors.forename: Colette
authors.initials: C
authors.lastname: Charpin
mesh_terms: D001943:Breast Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality*; D051929:CD146 Antigen / Q000032:analysis / Q000378:metabolism; D002277:Carcinoma / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality*; D051417:Focal Adhesion Kinase 1 / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053612:Janus Kinases / Q000032:analysis* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis* / Q000378:metabolism; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000378:metabolism; D015398:Signal Transduction; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D051929:CD146 Antigen; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1; D053612:Janus Kinases; C496050:PTK2 protein, human