Phenotypic and genotypic characteristics of epidermal growth factor receptor (EGFR) in colorectal cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4110-4110
Author(s):  
G. A. Milano ◽  
M. C. Etienne-Grimaldi ◽  
M. Francoual ◽  
D. Benchimol ◽  
M. Chazal ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Copy Number ◽  
Binding Assay ◽  
Gene Copy Number ◽  
Normal Mucosa ◽  
Gene Copy ◽  
Colorectal Tumors ◽  
Egfr Gene ◽  
Egfr Expression ◽  
The Mean

4110 Background: Colorectal tumors express EGFR and are responsive to anti-EGFR therapies. However, there is no tumoral predictive factor for anti-EGFR therapy in colorectal cancer and EGFR gene copy number is currently a good candidate. The aim of this study was to examine relationships between EGFR germinal polymorphisms, EGFR gene copy number and EGFR expression. Methods: Eighty primary colorectal tumors were analyzed along with 39 normal mucosas. Tumor staging was : 4 stage 0, 13 stage I, 22 stage II, 23 stage III and 18 stage IV. EGFR -216G>T and -191C>A genotypes were analyzed by PCR-RFLP, CA-repeats polymorphism in intron 1 by fluorescent genotyping and gene copy number was measured by PCR amplification. EGFR expression was quantified with the reference Scatchard binding assay giving high- and low-affinity sites along with Kd values (Francoual M et al. Ann Oncol 17, 2006). Results: The number of CA- repeats varied from 14 to 21. Considered genotypes were superimposable between tumoral and normal tissues. A linkage disequilibrium was noted between -216G>T and -191C>A genotypes (p = 0.011). CA-repeats polymorphism and -216G>T genotype were not independent (p = 0.002). No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene amplification. EGFR gene amplification in tumor and normal tissue varied over a 4.7- and 2.9-fold range, respectively, and were not correlated. The mean value of the tumor/normal mucosa amplification ratio was 1.16 (range 0.55–2.68) and 14% of patients exhibited lower amplification in the tumor relative to the normal mucosa (ratio < 0.75). The mean ratio of high-affinity sites between tumor and normal mucosa was 1.20 (range 0.03–13.33). Conclusions: In colorectal tumors, neither EGFR gene amplification nor EGFR germinal gene polymorphisms influenced EGFR expression quantified with a specific ligand-binding assay. No significant financial relationships to disclose.

Gene copy number of epidermal growth factor receptor (EGFR) by fluorescent in situ hybridization (FISH) in head and neck squamous cell carcinomas (HNSCC) is closely correlated with EGFR protein levels assessed by automated quantitative protein analysis (AQUA)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6023-6023
Author(s):  
P. Weinberger ◽  
A. Psyrri ◽  
P. Kountourakis ◽  
T. Rampias ◽  
C. Sasaki ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Protein Expression ◽  
Protein Content ◽  
Gene Amplification ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Egfr Gene ◽  
Protein Levels

6023 Background: EGFR overexpression correlates with recurrence and with treatment resistance in HNSCC. The mechanisms of EGFR protein overexpression are poorly understood. Nonetheless, previous investigators have not demonstrated a correlation between EGFR gene copy number and protein content, using conventional immunohistochemistry (IHC). The aim of this study was to evaluate the relationship of EGFR gene copy number and protein expression utilizing fluorescence in situ hybridization (FISH) and AQUA, a novel, immunohistochemical method of automated quantitative in situ proteomic analysis which permits subcellular localization. Methods: A tissue microarray composed of 137 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis/Abbot) and EGFR protein expression (DAKO antibody) using AQUA analysis of EGFR staining scored on a scale of 0–255 and by conventional IHC. Agreement was assessed using kappa. Results: Sixteen (15%) of one-hundred six tumors with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH+). AQUA demonstrated a range of 3.6–102.2; protein levels assessed by AQUA in the FISH amplified cases were significantly higher (p =0.008) than in the FISH non- amplified ones. Using the EGFR 75th percentile as a cut-off, AQUA and FISH showed significant agreement (percentage of overall agreement 82%, kappa=0.458, p=0.003). To the contrary there was no concordance between FISH and conventional IHC results in this series. Conclusions: The discrepancy between EGFR gene amplification rate and protein expression by IHC reported previously may be due to the limitations and nonquantitative nature of conventional IHC. EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. No significant financial relationships to disclose.

scholarly journals EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer

2011 ◽  
Vol 105 (2) ◽  
pp. 255-262 ◽  
Author(s):  
A Ålgars ◽  
M Lintunen ◽  
O Carpén ◽  
R Ristamäki ◽  
J Sundström
Keyword(s):  
Colorectal Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Egfr Gene ◽  
Egfr Expression

EGFR, HER2, and phospho-Akt are not predictive factors for response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7111-7111 ◽  
Author(s):  
L. Toschi ◽  
G. Metro ◽  
E. Magrini ◽  
S. Bartolini ◽  
C. Ligorio ◽  
...  
Keyword(s):  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
First Line ◽  
Her2 Gene ◽  
Egfr Gene ◽  
Egfr Expression ◽  
Response To Chemotherapy ◽  
Egfr Tki ◽  
Line Chemotherapy

7111 Background: Response to Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is significantly associated with increased EGFR gene copy number, increased EGFR expression or presence of activating EGFR gene mutations. In presence of EGFR, increased HER2 gene copy number, as well as activation of the anti-apoptotic protein Akt demonstrated to increase EGFR-TKI sensitivity in both clinical and preclinical models. Aim of the present study was to assess whether these biomarkers also associate with response to first-line chemotherapy. Methods: Patients with advanced NSCLC with full clinical data and with tumor tissue available were selected for this analysis. Specimens were evaluated for EGFR and HER2 gene copy number by FISH, EGFR and p-AKT protein expression by immunohistochemistry. RECIST criteria were used to assess response to chemotherapy. Results: A total of 144 NSCLC were included in this analysis. Patient characteristics included: male/female: 95/49; PS 0/1/2: 112/29/3; stage III/IV: 44/100; adenocarcinomas plus bronchioloalveolar/squamous/other: 86/35/23; never/former/current smokers: 26/69/49. The majority of patients were treated with first-line platinum-based chemotherapy (115/79.9%). Response to chemotherapy was not associated with any clinical characteristic. A trend towards better response was observed in non-adenocarcinoma histologies (p = 0.08) and in smokers (p = 0.20). Response and time to disease progression (TTP) were not influenced by EGFR/HER2 FISH status, nor P-Akt/EGFR expression. In EGFR FISH positive response rate was 36.4% and TTP was 6.4 months, versus 28.7% and 7.3 months in EGFR FISH negative (p = 0.4 for both). Conclusions: Biomarkers useful for selection of patients candidate for TKI therapy are not predictive for response to first-line chemotherapy in NSCLC. No significant financial relationships to disclose.

Correlation of the EGFR gene mutation, gene amplification and protein expression in non-small cell lung cancer with clinical outcomes of erlotinib monotherapy: An exploratory analysis of biomarkers by the Korean Cancer Study Group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7608-7608
Author(s):  
M. Ahn ◽  
J. Ahn ◽  
S. Kim ◽  
H. Kim ◽  
J. Lee ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Copy Number ◽  
Advanced Nsclc ◽  
Gene Copy Number ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Egfr Gene ◽  
Cancer Study Group ◽  
Rate Of Response ◽  
Egfr Gene Mutation

7608 Background: Mutations in epidermal growth factor receptor (EGFR) are considered to be strong predictive marker for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. The aim of this study conducted by the Korean Cancer Study Group (KCSG) was to determine the clinical implications of EGFR gene mutation, increased gene copy number or protein over- expression in Korean patients with advanced NSCLC who had been treated with erlotinib. Patients and Methods: A total of 120 patients received erlotinib at a dose of 150 mg daily as part of an open label phase II monotherapy trial between January 2005 and May 2006 in Korea. Ninety-two tissue samples obtained from these patients were analyzed for EGFR mutations (exon 18–21), 88 samples for EGFR gene amplification by real time PCR, and 77 samples for EGFR protein expression by immunohistochemical (IHC) staining. Results: Twenty-four out of 92 patients (26.1%) had EGFR mutations in exon 18, 19, or 21, most commonly in exon 19 (75%, 18/24). A higher frequencies were noted in female patients (40.0% vs 17.5%, p=0.017). Higher rate of response to erlotinib was noted in patients with EGFR mutations compared to wild type (N=14/24 (58.3%) vs 11/68 (16.2%), p<0.001). With the median follow-up duration of 14.5 months, time to progression (TTP) and overall survival (OS) were also significantly longer in patients with mutations than those without mutations (p=0.003, p=0.042). Increased EGFR gene copy number was found in 44.9% (36/88). Patients with increased gene copy number achieved higher rate of response to erlotinib (N=14/36 (38.9%) vs 9/52 (17.3%), p=0.023). Also patients with high gene copy number showed longer TTP and OS (p<0.001, p=0.022). Forty six out of 75 patients showed (+) IHC staining for EGFR protein although there was no relationship between the EGFR expression and the response to erlotinib, TTP or OS (p=0.82, p=0.35, p=0.83). Conclusion: EGFR mutation and gene amplification were shown to be important predictive markers not only for response but also for survival of the Korean patients with advanced NSCLC who had been treated with erlotinib. No significant financial relationships to disclose.

scholarly journals Increased MET Gene Copy Number Negatively Affects Survival of Surgically Resected Non–Small-Cell Lung Cancer Patients

2009 ◽  
Vol 27 (10) ◽  
pp. 1667-1674 ◽  
Author(s):  
Federico Cappuzzo ◽  
Antonio Marchetti ◽  
Margaret Skokan ◽  
Elisa Rossi ◽  
Sujatha Gajapathy ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Gene Amplification ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Small Cell ◽  
Gene Copy ◽  
Small Cell Lung ◽  
Egfr Gene

Purpose To investigate the prognostic role of genomic gain for MET and epidermal growth factor receptor (EGFR) genes in surgically resected non–small-cell lung cancer (NSCLC). Patients and Methods This retrospective study included 447 NSCLC patients with available tumor tissue from primary lung tumor and survival data. EGFR and MET status was evaluated by fluorescent in situ hybridization (FISH) in tissue microarray sections. Results EGFR FISH results were obtained in 376 cases. EGFR gene amplification and high polysomy (EGFR FISH+) were observed in 10.4% and 32.4% of cases, respectively. EGFR FISH-positive patients had a nonsignificant shorter survival than EGFR FISH-negative patients (P = .4). Activating EGFR mutations were detected in 9.7% of 144 stage I-II disease with no impact on survival. MET FISH analysis was performed in 435 cases. High MET gene copy number (mean ≥ 5 copies/cell) was observed in 48 cases (MET+, 11.1%), including 18 cases with true gene amplification (4.1%). MET+ status was associated with advanced stage (P = .01), with grade 3 (P = .016) and with EGFR FISH+ result (P < .0001). No patient with activating EGFR mutation resulted MET+. In the whole population, MET-positive patients had shorter survival than MET-negative patients (P = .005). Multivariable model confirmed that MET-negative patients had a significant reduction in the risk of death than MET-positive patients (hazard ratio, 0.66; P = .04). Conclusion MET increased gene copy number is an independent negative prognostic factor in surgically resected NSCLC. EGFR gene gain does not impact survival after resection.

MET Gene High Copy Number (Amplification/Polysomy) Identified in Melanoma for Potential Targeted Therapy

2021 ◽  
Author(s):  
Nisha S Ramani ◽  
Ajaykumar C Morani ◽  
Shengle Zhang
Keyword(s):  
Targeted Therapy ◽  
Gene Amplification ◽  
Copy Number ◽  
Kinase Inhibitors ◽  
Gene Copy Number ◽  
Tissue Microarrays ◽  
High Copy Number ◽  
Gene Copy ◽  
Aberrant Expression ◽  
Mesenchymal Epithelial Transition Factor

Abstract Objectives Aberrant expression of the mesenchymal epithelial transition factor (MET) gene has been observed in several malignancies, and drugs targeting the MET gene have been implicated in clinical trials with promising results. Hence, MET is a potentially targetable oncogenic driver. We explored the frequency of MET gene high copy number in melanomas and carcinomas. Methods The study group included 135 patients. Tissue microarrays were constructed with 19 melanomas and 116 carcinomas diagnosed from 2010 to 2012. We screened MET gene copy number by fluorescence in situ hybridization analysis using probes for MET gene and CEP7 as control. Results We found MET gene amplification in 2 (11%) of 19 melanoma cases, whereas 5 (26%) of 19 melanoma cases showed polysomy. For carcinomas, there was no MET gene amplification identified. However, 8 (7%) of 116 cases showed polysomy. Conclusions In our study, MET gene amplification was identified in 11% of melanomas and is relatively concordant with few reported studies. However, about 26% of the additional melanoma cases showed MET gene polysomy, which has not been reported as per our knowledge. If these results are validated with further orthogonal studies, more of the melanoma cases could potentially benefit from targeted therapy with MET tyrosine kinase inhibitors.

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