30 January 2007
Inflammatory breast cancer treatment target proposed
Researchers have highlighted a possible treatment target for inflammatory breast cancer (IBC) after detecting specific c-Met overexpression in such tumors.
"Inflammatory breast cancers (IBC) are very aggressive tumors that most often develop in young women and are associated with poor 5-year survival ranging from 30 to 50%," note the study authors.
Deregulation of c-Met has been shown to correlate with a poor outcome in breast carcinomas, and various c-Met inhibitors have recently been developed as potential drugs for such cancers, they add.
To further explore this issue, Colette Charpin-Taranger, from the Centre Hospitalo-Universitaire Nord in Marseille, France, and colleagues compared expression of c-Met , PI3K, and E-cadherin in tumor samples from 41 women with IBC and 480 with non-IBC ducal breast carcinomas, who served as controls.
The team constructed tissue microarrays for tumor sample examination and quantified c-Met immunoprecipitates within the tumor using image analysis software.
Results revealed significant overexpression of c-Met in IBC compared with non-IBC samples, with averages of 21.3% versus 2.7% of their surfaces immunostained.
Women with IBC also showed significant overexpression of PI3K compared with controls, with 19.6% versus 4.4% of their tumor samples immunostained.
These findings suggest "that the overexpressed c-Met is functionally active at least through the PI3K signal transduction pathway," say the investigators.
Finally, the percentage of E-cadherin-positive surfaces was significantly higher among samples from women with IBC than controls, at 35.4% versus 10.3%.
"Our results confirm that c-Met and PI3K are significantly overexpressed in IBC, suggesting that in this particular clinical setting, c-Met expression and downstream signal transducers may be regarded as potential targets for specific therapies," states the team.
"Also, overexpression of c-Met as well as E-cadherin appears to belong to the proteomic signature of IBC," the researchers conclude.
Br J Cancer 2007; 96: 329-335
http://www.nature.com/bjc/journal/v9.../6603569a.html
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