Epidermal Growth Factor Receptor Copy Number Alterations Correlate With Poor Clinical Outcome in Patients With Head and Neck Squamous Cancer

2007 ◽  
Vol 25 (16) ◽  
pp. 2164-2170 ◽  
Author(s):  
Stephane Temam ◽  
Hidetoshi Kawaguchi ◽  
Adel K. El-Naggar ◽  
Jaroslav Jelinek ◽  
Hongli Tang ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Copy Number Alterations ◽  
Egfr Gene ◽  
Copy Numbers ◽  
Epidermal Growth ◽  
Gene Copy Numbers

Purpose Overexpression of epidermal growth factor receptor (EGFR) is common in head and neck squamous cell carcinoma (HNSCC). Recent studies showed that EGFR inhibitors are effective for patients with HNSCC. This study analyzed the genetic nature of EGFR gene in HNSCC and its clinical correlations. Patients and Methods The EGFR gene copy numbers in 134 HNSCC tumors were determined using quantitative real-time polymerase chain reaction. The status of EGFR gene copy numbers was analyzed with clinical parameters including clinical outcome. Mutation status of EGFR exons 18, 19, and 21 was determined in the HNSCC tumors. Results Aberrant EGFR copy numbers were found in 32 (24%) of 134 tumors, including 22 (17%) with increased copy number and 10 (7%) with decreased copy number. Patients whose tumors had EGFR copy number alterations (particularly patients with increased copy numbers) had significantly poorer overall, cancer-specific, and disease-free survivals compared with patients with normal copy numbers (P < .0001). At 5 years after initial diagnosis, 20 (91%) of the 22 patients with increased copy numbers died of disease compared with 30 (29%) of the 102 patients with normal copy number. No mutations on EGFR exons 18, 19, and 21 were detected in any of the tumors. Conclusion A subset of HNSCC manifests EGFR copy number alterations, and this is associated with a poor clinical outcome, suggesting a biologic role of the alterations. The rare mutation or small deletion at EGFR exons 18 to 21 indicates a minimal role of these events in HNSCC.

Correlation between epidermal growth factor receptor gene status and clinical outcome of gefitinib in Japanese patients with non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7192-7192 ◽  
Author(s):  
K. Kasahara ◽  
T. Sone ◽  
H. Kimura ◽  
K. Nishio ◽  
T. Tamura ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Gene Copy ◽  
Egfr Gene ◽  
Copy Numbers ◽  
Epidermal Growth ◽  
Gene Status ◽  
Gene Copy Numbers

7192 Background: Epidermal growth factor receptor (EGFR) gene amplification and mutation have been reported to be predictors of response to EGFR inhibitors. We evaluated EGFR gene copy number and mutations in biopsy samples of non-small cell lung cancer (NSCLC) treated with gefitinib (G) and analyzed the correlation between gene status and clinical outcome. Methods: EGFR gene copy numbers in biopsy samples were evaluated using FISH and categorized as described by Cappuzzo et al. We also performed mutational analysesof exons 18, 19 and 21 of EGFR by PCR and direct sequencing. Response was judged using the RECIST guidelines. Time to progression (TTP) and overall survival (OS) were calculated and evaluated by the Kaplan-Meier method. Groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. Results: Of 59 patients (pts) enrolled in this investigation, 24 pts (41%) were female and 21 pts (35%) had never smoked. The most common histological subtype was adenocarcinoma (73%) and 36 pts (61%) had good PS 0–1. Gene copy numbers could be analyzed in 54 pts. Gene amplification was observed in 21 pts, high polysomy in 5 pts, low polysomy in 18 pts, low trisomy in 5 pts and disomy in 5 pts. FISH positivity was observed in 26 pts (48%). EGFR mutations were detected in 18 pts (31%); point mutations in exon 21 were observed in 5 pts, in-frame deletions in exon 19 in 12 pts, a point mutation in exon 18 in 1 pt. Response rate in pts with EGFR mutations was significantly higher than in pts without mutations (56% vs. 15%, p = .0011). Response rate in FISH-positive pts was 31% and that in FISH-negative pts was 21%, the association with response was not significant. EGFR mutations were also correlated with improved TTP (median 8.3 m vs. 1.8 m, p = .0014) and OS (median 18.8 m vs. 6.4 m, p = .0059). There were no significant differences in TTP and OS based on FISH positivity. On multivariable analysis, EGFR mutations remained significantly associated with improved TTP and OS. Conclusions: Our results suggest that EGFR mutations are a better predictor of clinical benfit of G when compared with gene copy number in Japanese NSCLC pts. [Table: see text]

Epidermal Growth Factor Receptor in Non–Small-Cell Lung Carcinomas: Correlation Between Gene Copy Number and Protein Expression and Impact on Prognosis

2003 ◽  
Vol 21 (20) ◽  
pp. 3798-3807 ◽  
Author(s):  
Fred R. Hirsch ◽  
Marileila Varella-Garcia ◽  
Paul A. Bunn ◽  
Michael V. Di Maria ◽  
Robert Veve ◽  
...  
Keyword(s):  
Protein Expression ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Protein Status ◽  
Copy Numbers ◽  
High Gene ◽  
Epidermal Growth ◽  
Gene Copy Numbers

Purpose: The epidermal growth factor receptor (EGFR) is frequently overexpressed in non–small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood. Materials and Methods: Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies. Protein expression was assessed by immunohistochemistry on a scale from 0 to 400 (percentage of positive cells × staining intensity). Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). Results: EGFR protein overexpression was observed in 62% of the NSCLC (25% scored 201 to 300; 37% scored 301 to 400), more frequently in SCC than non-SCC (82% v 44%; P < .001), and in 80% of the bronchioloalveolar carcinomas. The prevalent FISH patterns were balanced disomy (40%) and trisomy (38%) for EGFR gene and chromosome 7 (40%), whereas balanced polysomy was seen in 13% and gene amplification was seen in 9% of the patients. Gene copy number correlated with protein expression (r = 0.4; P < .001). EGFR overexpression or high gene copy numbers had no significant influence on prognosis. Conclusion: EGFR overexpression is frequent in NSCLC, is most prominent in SCC, and correlates with increased gene copy number per cell. High gene copy numbers per cell showed a trend toward poor prognosis. It will be important to evaluate EGFR gene and EGFR protein status and signal protein expression to properly interpret future clinical trials using EGFR inhibitors.

Prognostic value of epidermal growth factor receptor gene amplification in surgically resected non-adenocarcinoma lung cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18553-e18553
Author(s):  
Yaewon Yang ◽  
Hyun Chang ◽  
Jong-Seok Lee ◽  
YuJung Kim ◽  
Sang-hoon Jheon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Egfr Gene ◽  
Epidermal Growth

e18553 Background: The purpose of this study is to investigate the prognostic role of genomoic gain and expression for epidermal growth factor receptor (EGFR) gene in surgically resected non-adenocarcinoma of non-small-cell lung cancer (NA-NSCLC). Methods: This retrospective study included 115 NA-NSCLC consecutive patients with available tumor tissue and survival data, median follow up period of 6.4 years. EGFR gene copy number and protein expression was evaluated using by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in tissue microarray sections, respectively. Results: Among 115 patients, 99 patients (86.1 %) were with squamous cell carcinoma histology. EGFR gene amplification and high polysomy (EGFR FISH+) were observed in 57 (49.6%) and 45 (39.1%) patients, respectively. Patients with EGFR FISH+ had significantly shorter overall survival [median, 41 months vs. not reached (>70 months), P = 0.011]. Multivariable model confirmed that patients with EGFR FISH+ had a significantly greater risk of death than those with EGFR FISH-negative after adjusting pathologic staging, presence of pleural invasion, venous invasion and adjuvant chemotherapy (hazard ratio = 2.11, 95% confidence interval 1.23-3.61, P = 0.006). EGFR IHC expression did not associate with overall survival in same group. Conclusions: EGFR increased gene copy number is an independent negative prognostic factor in surgically resected NA-NSCLC.

Epidermal Growth Factor Receptor Gene Copy Number and Clinical Outcome of Metastatic Colorectal Cancer Treated With Panitumumab

2007 ◽  
Vol 25 (22) ◽  
pp. 3238-3245 ◽  
Author(s):  
Andrea Sartore-Bianchi ◽  
Mauro Moroni ◽  
Silvio Veronese ◽  
Carlo Carnaghi ◽  
Emilio Bajetta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Clinical Outcome ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Chromosome 7 ◽  
Gene Copy ◽  
Epidermal Growth

Purpose In a previous cohort study, we proposed that responsiveness of metastatic colorectal cancer (mCRC) to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies has a genetic basis, being associated with increased EGFR gene copy number (GCN) as measured by fluorescence in situ hybridization (FISH) in individual tumors. The present study was aimed at assessing the predictive role of EGFR GCN, in terms of clinical outcome, in patients treated with panitumumab. Patients and Methods Patients with mCRC refractory to standard therapies were a subset of patients from a phase III trial of panitumumab plus best supportive care (BSC; n = 58) versus BSC alone (n = 34) who were selected on the basis of availability of tumor samples adequate for FISH. Results In patients treated with panitumumab, a mean EGFR GCN of less than 2.5/nucleus or less than 40% of tumor cells displaying chromosome 7 polysomy within the tumor predicted for shorter progression-free survival (PFS; P = .039 and P = .029, respectively) and overall survival (P = .015 and P = .014, respectively). None of the treated patients with mean EGFR GCN of less than 2.47/nucleus or less than 43% of tumor cells displaying chromosome 7 polysomy obtained objective response compared with six of 20 and six of 19 patients with values greater than these cutoff limits, respectively (P = .0009 and P = .0007, respectively). Evaluation of BSC-treated patients showed no correlation between EGFR GCN or chromosome 7 polysomy status and PFS. Conclusion In a larger and more homogeneous series than in previous studies, present exploratory data suggest that mCRC patients with tumors distinguishable by FISH analysis of EGFR as homogenously disomic or with low chromosome 7 polysomy have a reduced likelihood of response to panitumumab.

Epidermal growth factor receptor (EGFR) gene copy number in colorectal adenoma-carcinoma progression

2012 ◽  
Vol 205 (12) ◽  
pp. 630-635 ◽  
Author(s):  
Marcella Flora ◽  
Simonetta Piana ◽  
Cristina Bassano ◽  
Alessandra Bisagni ◽  
Loredana De Marco ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Colorectal Adenoma ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Egfr Gene ◽  
Epidermal Growth
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