scholarly journals HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients

2013 ◽  
Vol 108 (3) ◽  
pp. 668-675 ◽  
Author(s):  
V Martin ◽  
L Landi ◽  
F Molinari ◽  
G Fountzilas ◽  
R Geva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Clinical Efficacy ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Her2 Gene ◽  
Colorectal Cancer Patients

EGFR, HER2 and Kras as predictive factors for cetuximab sensitivity in colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4021-4021 ◽  
Author(s):  
G. Finocchiaro ◽  
F. Cappuzzo ◽  
P. A. Jänne ◽  
K. Bencardino ◽  
C. Carnaghi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Her2 Gene ◽  
Primary Tumors ◽  
Biomarker Analysis ◽  
Colorectal Cancer Patients

4021 Background: In colorectal cancer, biological mechanisms underlying response or resistance to cetuximab, a monoclonal antibody against the extracellular domain of the EGFR are not defined. Small retrospective studies suggested that EGFR increased gene copy number measured by fluorescence in situ hybridization (FISH) or presence of KRAS mutations were associated with cetuximab response or resistance, respectively. This study aimed to identify biological predictors for sensitivity/resistance to cetuximab treatment in colorectal cancer. We also compared biomarker results in primary tumors and corresponding metastases. Methods: We analyzed EGFR (IHC, FISH), HER2 (FISH), and KRAS (mutation) in paraffin embedded tumor blocks from 85 colorectal cancer patients treated with cetuximab. For FISH analyses, a positive result was defined according to criteria described in breast (Wolff et al. J Clin Oncol 2007), lung (Cappuzzo et al. JNCI 2005) and colorectal cancer (Moroni et al. Lancet Oncology 2005). EGFR, HER2 and PIK3CA mutation analyses are ongoing. Results: EGFR FISH positive patients (N=41), defined as ratio EGFR/nucleus =3, had a significantly higher RR (29.3% versus 6.8%, p=0.007) and TTP (6.6 versus 3.7 months, p=0.053) than EGFR FISH negative (N=44). No difference for clinical endpoints was observed using other scoring systems. EGFR expression assessed by IHC was not associated with any clinical end-point. Increased HER2 gene copy number was associated with shorter TTP (p=0.09) and survival (p=0.03). Compared to patients with wild type KRAS (N=49), KRAS mutation carriers (N=32) had a significantly lower RR (6.3% versus 26.5%, p= 0.02), shorter TTP (3.7 versus 6.3 months, p=0.07) and shorter survival (8.3 versus 10.8 months, p=0.2). In 22 patients with available primary and metastatic tumor tissue, there was no difference between these sites for EGFR FISH, HER2 FISH and KRAS results. Conclusions: This study, the largest biomarker analysis in colorectal cancer patients treated with cetuximab, shows a significant benefit in response and TTP for EGFR FISH positive patients. KRAS mutation analysis identifies a group of patients with the lowest chance to benefit from the therapy. Increased HER2 gene copy number predicts early escape from cetuximab therapy. No significant financial relationships to disclose.

scholarly journals Topoisomerase 1(TOP1 ) gene copy number in stage III colorectal cancer patients and its relation to prognosis

2012 ◽  
Vol 7 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Maria Unni Rømer ◽  
Sune Boris Nygård ◽  
Ib Jarle Christensen ◽  
Signe Lykke Nielsen ◽  
Kirsten Vang Nielsen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Gene Copy Number ◽  
Stage Iii ◽  
Gene Copy ◽  
Topoisomerase 1 ◽  
Colorectal Cancer Patients

Epidermal growth factor gene amplification is not frequent and cannot account for antitumor activity of cetuximab plus chemotherapy in advanced colorectal cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3561-3561 ◽  
Author(s):  
C. Garufi ◽  
M. Mottolese ◽  
A. Cianciulli ◽  
M. Zeuli ◽  
S. Buglioni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Cancer Patients ◽  
Copy Number ◽  
Advanced Colorectal Cancer ◽  
Gene Copy Number ◽  
Chromosome 7 ◽  
Gene Copy ◽  
Egfr Gene ◽  
Colorectal Cancer Patients

3561 Cetuximab has been shown to be active in the metastatic colorectal cancer, but EGFR detection by immunohistochemistry is not predictive for tumor response. Moroni et al (Lancet Oncology 2005) showed that, in patients responsive to Cetuximab, EGFR gene copy number, assessed by FISH, was increased. On this basis, copy number and protein status of EGFR were investigated in 70 primary and/or metastatic colorectal carcinomas. Protein expression was assessed by immunohistochemistry (IHC) using DAKO EGFRPharmDX kit. Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). Dual-target, dual-color FISH assays were performed using the LSI EGFR SpectrumOrange/CEP 7 Spectrum Green probe. EGFR gene copy number, chromosome 7 copy number and the average EGFR gene to chromosome 7 signal ratio were reported as FISH genetic variables. Chromosome 7 was polysomic when cancer cells showed multiple centromere signals: low polysomy (2 to 5 signals), high polysomy (>5 signals). Samples with a ratio value ≥ 2.0 were considered to be amplified. EGFR protein was overexpressed in 57 out of 70 patients (81%). In the group of 58 patients evaluated as polysomic, 48 (82,7%) had a low polysomy level, whereas 20 (12.7%) had a high polysomy level. Gene amplification was seen only in 3/70 patients. High polysomy was evidenced only in the group of patients displaying an EGFR IHC score 2+/3+. Forty-six pretreated patients received a cetuximab-based treatment. Response to treatment has been already evaluated in 26 FISH-negative patients while for the other 20 it is still too early. We observed 7 PR (27%), 9 SD (35%) and 10 PD (38%). This study shows that in this series of advanced colorectal cancer patients, EGFR amplification, measured by FISH, is a rare event (4%) and could be considered together with chromosome 7 polysomy for the antitumor activity. No significant financial relationships to disclose.

Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number

2007 ◽  
Vol 15 (2) ◽  
pp. 649-654 ◽  
Author(s):  
Antoine Italiano ◽  
Philippe Follana ◽  
François-Xavier Caroli ◽  
Jean-Luc Badetti ◽  
Daniel Benchimol ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Fish Analysis ◽  
Egfr Gene ◽  
Colorectal Cancer Patients
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