Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas

Suzuki, Shioto; Dobashi, Yoh; Sakurai, Hiroyuki; Nishikawa, Keiichi; Hanawa, Masanori; Ooi, Akishi

doi:10.1002/cncr.20909

Cited by 115 publications

(115 citation statements)

References 77 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Expression of EGFR protein by immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization analysis had already been examined in these cases and described previously. 5 Profiles of these 28 cases examined in the present study are summarized in Table 1. At the time of surgery, none of the patients had received any treatment for lung cancer, including treatment with TKIs.…”

Section: Tissue Samples and Histological Classificationmentioning

confidence: 99%

“…In the previous studies, the intensity of EGFR immunoreactivity was scored using a four-tier system that we and others have established: negative, no discernible staining; 1 þ , definite cytoplasmic staining and/or equivocal discontinuous membrane staining; 2 þ , unequivocal membrane staining with moderate intensity; 3 þ , strong and complete membrane staining. 5,34 For the other proteins, p-Stat-3, p-Akt and p-Erk1/2, the intensity of reactivity was scored as positive ( þ ) or negative (À): positive ( þ ), definite nuclear staining with higher intensity than that of lymphocytes or endothelial cells which occasionally showed faint cytoplasmic staining; negative (À), no discernible staining or staining with lower intensity than those cells.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…5 Seven cases (25%) showed 2 þ staining confined to the cell membrane in more than 70% of the areas examined ( Figure 1a and b for Case 3), and five of them were known to harbor EGFR amplification (Figure 1d). 5 Six cases (21.4%) showed 1 þ staining both in the cell membrane as well as cytoplasm in 20-60% of the areas. The remaining 15 cases showed negative results ( Figure 2a and b for Case 8, Tables 1 and 2).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) has also been the target of cancer therapies owing to its critical role and for its frequent overexpression in many epithelial cancers, including non-small-cell lung cancer (NSCLC). 2,3,5,6 Our previous study showed that EGFR protein was overexpressed in 34% of NSCLC, and gene amplification was observed in 74% of EGFR-overexpressing tumors. 5 Nowadays, several EGFR-targeted therapies are in clinical use, including anti-EGFR monoclonal antibody cetuximab, as well as the tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib.…”

mentioning

confidence: 99%

“…2,3,5,6 Our previous study showed that EGFR protein was overexpressed in 34% of NSCLC, and gene amplification was observed in 74% of EGFR-overexpressing tumors. 5 Nowadays, several EGFR-targeted therapies are in clinical use, including anti-EGFR monoclonal antibody cetuximab, as well as the tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib. 2,7 Gefitinib has shown dramatic clinical responses in about 10-19% of NSCLC that had been refractory to conventional chemotherapy.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Diversity of epidermal growth factor receptor-mediated activation of downstream molecules in human lung carcinomas

et al. 2006

Self Cite

View full text Add to dashboard Cite

The correlations among epidermal growth factor receptor (EGFR) gene amplification, gene mutation, overexpression/phosphorylation of EGFR protein and activation of its downstream molecules, signal transducers and activators of transcription 3 (Stat-3), Akt and extracellular signal-related protein kinase 1/2 (Erk1/2) were investigated in 28 cases of human lung carcinomas. In five cases of carcinomas with EGFR amplification, EGFR expression and phosphorylation levels were higher than other cases, and Stat-3 was activated in all five cases. Point mutations in the tyrosine kinase domain of EGFR were detected in five cases, one of which was also associated with gene amplification. In these five cases, both EGFR expression and phosphorylation were enhanced, and Akt was activated in four cases. In the remaining 19 cases, EGFR protein expression was upregulated in eight cases and phosphorylated in four cases, but neither EGFR nor phosphorylated-EGFR expression levels specifically correlated with activation of particular downstream molecules. In general, either Stat-3 or Akt, but not both, was activated reciprocally and complementarily to each other, as indicated by their phosphorylation. However, Erk1/2 was activated regardless of the status of Stat-3, Akt or EGFR proteins. The current data suggest that persistent Stat-3 activation may be a critical event downstream of EGFR that has been overexpressed by gene amplification. In contrast, tumor cells harboring the EGFR mutation may persistently activate a cascade via Akt. Finally, in the majority of cases that have no aberration of the EGFR, its downstream molecules function in reciprocal and/or complementary manner in the maintenance and/or progression of carcinomas. These overall results could provide novel insights into potential chemotherapeutic regimens for lung carcinomas, such as inhibitors of Stat-3, Akt and Erk1/2.

show abstract

Section: Tissue Samples and Histological Classificationmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Diversity of epidermal growth factor receptor-mediated activation of downstream molecules in human lung carcinomas

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

Monitoring Conformational Changes in the Receptor Tyrosine Kinase EGFR

et al. 2016

View full text Add to dashboard Cite

The receptor tyrosine kinase EGFR is regulated by complex conformational changes, and this conformational control is disturbed in certain types of cancer. Many ligands are known to bind EGFR in its active conformation, thereby preventing ATP from binding. Only a few ligands are known to stabilize EGFR in its inactive conformation, thus providing novel strategies for perturbing EGFR activity. We report a direct binding assay that enables the identification of novel ligands that bind to and stabilize the inactive conformation of EGFR.

show abstract

Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas

Fukushima

Yoshino

Yano³

et al. 2007

Cancer

View full text Add to dashboard Cite

BACKGROUND. The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas. METHODS. A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor. RESULTS. Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P 5 .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level; <5 vs 5 <20 vs 20 5 35% vs 55% vs 87.5%, respectively, P 5 .040). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations (P 5 .036) with an odds ratio of 4.70 (95% confidence interval, 1.1-21.1). CONCLUSIONS. The serum CEA level appears to be closely associated with the presence of EGFR gene mutations in patients with pulmonary adenocarcinomas.

show abstract

Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas

Cited by 115 publications

References 77 publications

Diversity of epidermal growth factor receptor-mediated activation of downstream molecules in human lung carcinomas

Diversity of epidermal growth factor receptor-mediated activation of downstream molecules in human lung carcinomas

Monitoring Conformational Changes in the Receptor Tyrosine Kinase EGFR

Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas

Contact Info

Product

Resources

About