Epidermal Growth Factor Receptor (EGFR) mutation analysis, gene expression profiling and EGFR protein expression in primary prostate cancer

BMC Cancer

Research Article

Giorgia Migliardi¹  Caterina Peraldo-Neia²  Maurizia Mello-Grand³ 

[1] Department of Clinical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy;Department of Clinical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy;Laboratory of Cancer Genomics, "Fondazione Edo ed Elvo Tempia Valenta", Biella, Italy;Laboratory of Cancer Genomics, "Fondazione Edo ed Elvo Tempia Valenta", Biella, Italy;

关键词: Prostate Cancer;    Epidermal Growth Factor Receptor;    Gefitinib;    Gleason Score;    Epidermal Growth Factor Receptor Mutation;   

DOI  :  10.1186/1471-2407-11-31

 received in 2010-09-07, accepted in 2011-01-25,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundActivating 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.MethodsMutational 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.ResultsEGFR protein overexpression (EGFRhigh) was found in 36% of the tumour samples, and mutations were found in 13% of samples. Patients with EGFRhigh 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 (EGFRlow). Microarray analysis did not reveal any differences in gene expression between EGFRhigh and EGFRlow tumours. Conversely, in EGFRhigh 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/EGFRhigh (n=3) and mutated/EGFRlow 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.ConclusionsBased 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.

【 授权许可】

CC BY   
© Peraldo-Neia et al; licensee BioMed Central Ltd. 2011