[High-throughput quantification of tissue microarrays: identification of candidate target proteins in inflammatory breast cancer].
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.
Taranger-Charpin
Colette
C
Service de Pathologie (Anatomie et Cytologie Pathologiques) CHU Nord, chemin des Bour-reley, 13915 Marseille.
Andrac-Meyer
Lucile
L
Dales
Jean-Philippe
JP
Carpentier-Meunier
Séverine
S
Andonian
Claudine
C
Lavaut
Marie-Noelle
MN
Allasia
Claude
C
Bonnier
Pascal
P
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
D015820:Cadherins; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human