Journal
BMC CANCER
Volume 11, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1471-2407-11-31
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Funding
- Fondazione CRT, progetto Alfieri e Compagnia di San Paolo di Torino
- Fondazione Edo ed Elvo Tempia Valenta
- Compagnia di San Paolo di Torino
- Regione Piemonte
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Background: Activating mutations of the epidermal growth factor receptor (EGFR) confer sensitivity to the tyrosine kinase inhibitors (TKi), gefitinib and erlotinib. We analysed EGFR expression, EGFR mutation status and gene expression profiles of prostate cancer (PC) 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 tumour tissues derived from radical prostatectomy from 100 PC patients. Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples. Results: EGFR protein overexpression (EGFR(high)) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFR(high) tumours experienced a significantly increased risk of biochemical relapse (hazard ratio-HR 2.52, p=0.02) compared with patients with tumours expressing low levels of EGFR (EGFR(low)). Microarray analysis did not reveal any differences in gene expression between EGFR(high) and EGFR(low) tumours. Conversely, in EGFR(high) tumours, we were able to identify a 79 gene signature distinguishing mutated from non-mutated tumours. Additionally, 29 genes were found to be differentially expressed between mutated/EGFR(high) (n=3) and mutated/EGFR(low) tumours (n=5). Four of the down-regulated genes, U19/EAF2, ABCC4, KLK3 and ANXA3 and one of the up-regulated genes, FOXC1, are involved in PC 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 PC patients. Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.
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