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

Peraldo-Neia C, Migliardi G, Mello-Grand M, Montemurro F, Segir R, Pignochino Y, Cavalloni G, Torchio B, Mosso L, Chiorino G, Aglietta M - BMC Cancer (2011)

Bottom Line: Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.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.Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy. caterina.peraldoneia@ircc.it

ABSTRACT

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 (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.

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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Related in: MedlinePlus

Differentially expressed genes identified by microarray analysis were validated by relative qRT-PCR. White bars represent the average mRNA levels of each gene in EGFRlow class; gray bars represent the average mRNA levels of each gene in EGFRhigh class. Fold-change was calculated as described in "methods" section.
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Figure 7: Differentially expressed genes identified by microarray analysis were validated by relative qRT-PCR. White bars represent the average mRNA levels of each gene in EGFRlow class; gray bars represent the average mRNA levels of each gene in EGFRhigh class. Fold-change was calculated as described in "methods" section.

Mentions: Quantitative RT-PCR on 8 EGFR mutated samples confirmed results obtained by microarray analysis on the five differentially expressed genes discussed above (figure 7).


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

Peraldo-Neia C, Migliardi G, Mello-Grand M, Montemurro F, Segir R, Pignochino Y, Cavalloni G, Torchio B, Mosso L, Chiorino G, Aglietta M - BMC Cancer (2011)

Differentially expressed genes identified by microarray analysis were validated by relative qRT-PCR. White bars represent the average mRNA levels of each gene in EGFRlow class; gray bars represent the average mRNA levels of each gene in EGFRhigh class. Fold-change was calculated as described in "methods" section.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3040720&req=5

Figure 7: Differentially expressed genes identified by microarray analysis were validated by relative qRT-PCR. White bars represent the average mRNA levels of each gene in EGFRlow class; gray bars represent the average mRNA levels of each gene in EGFRhigh class. Fold-change was calculated as described in "methods" section.
Mentions: Quantitative RT-PCR on 8 EGFR mutated samples confirmed results obtained by microarray analysis on the five differentially expressed genes discussed above (figure 7).

Bottom Line: Gene expression profiling using oligo-microarrays was also carried out in 51 of the PC samples.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.Having been generated in a relatively small sample of patients, our results warrant confirmation in larger series.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy. caterina.peraldoneia@ircc.it

ABSTRACT

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 (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.

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.

Show MeSH
Related in: MedlinePlus