Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors

Italiano, Antoîne; Vandenbos, Fanny; Otto, Josiane; Mouroux, Jérôme; Fontaine, Denys; Marcy, Pierre-Yves; Cardot, Nathalie; Thyss, Antoine; Pédeutour, Florence

doi:10.1093/annonc/mdl038

Cited by 122 publications

(91 citation statements)

References 20 publications

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“…17,20,31 We and others have previously shown that the correlation between increased EGFR gene copy number per cell and EGFR protein expression is not absolute in lung squamous cell carcinoma and adenocarcinoma. 5,31 Our additional results concerning lung SC underscores the potential crucial role, in this group of tumors, of mechanisms controlling EGFR expression unrelated to the number of genes per cell, such as post-transcriptional regulation. Moreover, none of the cases included in our series harbored EGFR mutations.…”

Section: Discussionmentioning

confidence: 96%

“…Tumors were considered positive for EGFR when at least 10% of the tumor cells had membranous staining. 17,31 Cytoplasmic staining without associated membrane staining was reported as negative. Staining intensity was defined as negative (0), weak (11), moderate (21) or strong (31).…”

Section: Patientsmentioning

confidence: 99%

“…The procedure for deparaffinization and FISH was done as described previously. 31 The 5-lm sections were dewaxed for 3 3 10 min in xylene, washed in 100% ethanol, air dried and incubated in 2 3 sodium saline citrate (SSC) at 75°C for 20 min and a proteinase K solution (Roche, Meylan, France) (20 U/ml in 2 3 SSC) at 45°C for 50 min. Then, they were washed in 2 3 SSC for 5 min at room temperature and stored in 70% ethanol at 4°C before hybridization with the LSI EGFR SpectrumOrange/CEP 7 SpectrumGreen probe (Vysis, Abbott Laboratories, Rungis, France) according to the manufacturer's instructions.…”

Section: Egfr Gene Copy Number Evaluationmentioning

confidence: 99%

“…Gene amplification was defined by the presence of tight gene clusters, and a gene/chromosome per cell ratio 2 or 15 copies of the gene per cell in 10% of analyzed cells. 13,17,31 EGFR mutational status For mutation detection, DNA was extracted from the areas of fresh formalin fixed, paraffin-embedded tumor sections. EGFR mutations were detected using PCR-based direct sequencing of exons 18-21 using primers and annealing conditions as described by Pao et al 32 Aliquots of PCR products were examined by electrophoresis on 2% agarose gel containing ethidium bromide.…”

Section: Egfr Gene Copy Number Evaluationmentioning

confidence: 99%

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EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: Implications for anti‐EGFR treatment of a rare lung malignancy

Italiano

Cortot

Ilié

et al. 2009

Intl Journal of Cancer

103

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Sarcomatoid carcinomas (SC) of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous cell components and characterized by a more aggressive outcome than other histological subtypes of nonsmall cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR)‐targeted therapies have emerged as a promising therapeutic approach in patients with advanced typical NSCLC such as adenocarcinoma, the potential clinical activity of these drugs in lung SC is still unknown. To investigate this point, we have analyzed the status of 4 EGFR pathways biomarkers in a series of lung SC. EGFR protein expression, EGFR gene copy number, EGFR mutational status and KRAS mutational status were assessed in a series of 22 consecutive cases of primary lung SC. EGFR protein overexpression was observed in all the cases. High level of polysomy (≥4 copies of the gene in >40% of cells) was detected in 5 cases (23%). No EGFR mutation was detected. KRAS mutations were found in 8 patients (38%; Gly12Cys in 6 cases and Gly12Val in 2 cases). The consistent EGFR protein overexpression and the high rate of KRAS mutation may contribute to the poorer outcome of lung SC in comparison with typical NSCLC. The rare incidence of increased EGFR gene copy number, the lack of EGFR mutation and the high rate of KRAS mutation observed in our series also suggest that most patients with lung SC are not likely to benefit from anti‐EGFR therapies. © 2009 UICC

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Section: Discussionmentioning

confidence: 96%

Section: Patientsmentioning

confidence: 99%

Section: Egfr Gene Copy Number Evaluationmentioning

confidence: 99%

Section: Egfr Gene Copy Number Evaluationmentioning

confidence: 99%

See 2 more Smart Citations

EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: Implications for anti‐EGFR treatment of a rare lung malignancy

Italiano

Cortot

Ilié

et al. 2009

Intl Journal of Cancer

103

View full text Add to dashboard Cite

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“…Moreover, the vast majority of studies have only reported EGFR status in the primary tumor even though the main targets of NSCLC therapy are the metastases themselves. Italiano et al 86 were the first group to question the stability of EGFR expression during the NSCLC metastatic process. EGFR status, confirmed by IHC and FISH, was found to vary significantly between primary NSCLC and distant metastasis.…”

Section: Correlation Between Primary Tumor and Metastases Alterationsmentioning

confidence: 99%

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

Ulivi

Calistri

Zoli

et al. 2010

J Nucleic Acids Invest

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In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma-or serum-derived DNA.

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Risk factors for brain metastases in patients with non–small‐cell lung cancer

Wang

et al. 2018

Cancer Medicine

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Brain metastases (BM) are severe incidents in patients with non–small‐cell lung cancer (NSCLC). The controversial value of prophylactic cranial irradiation (PCI) in NSCLC in terms of survival benefit prompted us to explore the possible risk factors for BM in NSCLC and identify the potential population most likely to benefit from PCI. Risk factors for brain metastases in NSCLC are reviewed in this article. Identifying patients with a higher risk of BM could possibly increase the benefit of PCI while reducing the discomfort and risks caused by unnecessary invasive procedures in the NSCLC patient population. Future studies might focus on finding a solid basis for the prediction of the occurrence of brain metastases and for the therapeutic decision on the use of PCI.

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Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors

Abstract: EGFR expression is not stable during metastatic progression in a significant proportion of NSCLC. These findings have to be considered in future prospective studies.

Cited by 122 publications

References 20 publications

EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: Implications for anti‐EGFR treatment of a rare lung malignancy

EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: Implications for anti‐EGFR treatment of a rare lung malignancy

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

Risk factors for brain metastases in patients with non–small‐cell lung cancer

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