@entity470 (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary XXXX .

@entity1 @entity263 @entity4562 @entity470 @entity5 @entity1486 @entity17967 @entity73233 @entity36620 @entity669 @entity41784 @entity3866
BACKGROUND: Activating mutations of the @entity470 (EGFR) confer sensitivity to the @entity669 kinase inhibitors (TKi), @entity4562 and @entity3866 . We analysed EGFR expression, EGFR mutation status and gene expression profiles of @entity263 ( @entity263 ) to supply a rationale for EGFR targeted therapies in this disease. METHODS: Mutational analysis of EGFR TK domain (exons from 18 to 21) and immunohistochemistry for EGFR were performed on @entity5 tissues derived from radical prostatectomy from 100 @entity263 @entity1 . Gene expression profiling using oligo-microarrays was also carried out in 51 of the @entity263 samples. RESULTS: EGFR protein overexpression (EGFRhigh) was found in 36% of the @entity5 samples, and mutations were found in 13% of samples. @entity1 with EGFRhigh @entity5 experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with @entity1 with @entity5 expressing low levels of EGFR (EGFRlow). Microarray analysis did not reveal any differences in gene expression between EGFRhigh and EGFRlow @entity5 . Conversely, in EGFRhigh @entity5 , we were able to identify a 79 gene signature distinguishing mutated from non-mutated @entity5 . Additionally, 29 genes were found to be differentially expressed between mutated/EGFRhigh (n=3) and mutated/EGFRlow @entity5 (n=5). Four of the down-regulated genes, @entity73233 / @entity73233 , @entity36620 , @entity1486 and @entity41784 and one of the up-regulated genes, @entity17967 , are involved in @entity263 progression. CONCLUSIONS: Based on our findings, we hypothesize that accurate definition of the EGFR status could improve prognostic stratification and we suggest a possible role for EGFR-directed therapies in @entity263 @entity1 . Having been generated in a relatively small sample of @entity1 , our results warrant confirmation in larger series.
