FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors
© BioMed Central Ltd 2009
Published: 21 April 2009
In their report, Götte and coworkers  analyzed the expression of c-Met in 200 patients with ductal carcinoma in situ. They concluded that c-Met could be related to angiogenic and lymphangiogenic factors in ductal carcinoma in situ. On the other hand, Greenberg and coworkers  studied 31 patients with ductal infiltrating carcinoma (DIC) to detect c-Met expression in their axillary fluids. They observed a correlation of c-Met expression with increasing tumor size and grade, capillary and lymphatic invasion and lymph node metastasis.
We applied the fluorescent in situ hybridization (FISH) technique using the LSI D7S486/CEP7 commercial probe (Abbott Molecular Inc., Des Plaines, IL, USA), which includes the MET gene, and immunohistochemistry using c-Met monoclonal antibody clone 3D4 (Invitrogen, Carlsbad, CA, USA) to 184 archival invasive breast tumors (93 DIC and 91 lobular carcinomas). We constructed ten tissue microarrays with three replicates per sample. Pearson's chi-squared and Fisher's exact test were used to analyze the results.
Results of IHC of c-Met and FISH of LSI D7S486/CEP7 applied to lobular and ductal carcinomas
FISH + IHC
PE + P
IHC and FISH results of MET according to the status of PR receptor in DIC carcinomas
ER+/PR+ (n = 46)
ER+/PR- (n = 34)
We can conclude that amplification of MET in breast cancer is not a common event, as opposed to other cancer subtypes (renal, gastric and lung carcinomas). Although found in breast tumors, it seems that overexpression of c-Met is not mainly due to increassed gene copy number of MET/polysomy7. However, polysomy in the ER+/PR- group could be an important mechanism – although not the only one – responsible for the differential expression observed in this type of DIC. This c-Met overexpression and the presence of polysomy 7 could be important events to be considered with regard to the known poor response to endocrine therapies of ER+/PR- breast tumors. Lack of PR expression in ER+ tumors may be a surrogate marker of aberrant growth factor signaling  that could be associated with their more aggressive outcome, as has already been described .
Our study suggests that it would be interesting to investigate new therapeutic options for ER+/PR- DIC, which may include c-Met inhibitors.
ductal infiltrating carcinoma
fluorescent in situ hybridization
Grants PI05/0961 and PI06/1513 from Ministerio de Sanidad y Consumo ISCIII and RTICC 06/0020/19. Tumoral samples belong to the 'Xarxa de Banc de Tumors de Catalunya' (XBTC).
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