Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis.
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.
Garcia
Stéphane
S
Department of Pathology, Centre Hospitalo-Universitaire, Hôpital Nord, Marseille, France.
Dales
Jean-Philippe
JP
Charafe-Jauffret
Emmanuelle
E
Carpentier-Meunier
Séverine
S
Andrac-Meyer
Lucile
L
Jacquemier
Jocelyne
J
Andonian
Claudine
C
Lavaut
Marie-Noelle
MN
Allasia
Claude
C
Bonnier
Pascal
P
Charpin
Colette
C
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
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