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Vlems, F.A., Ladanyi, A., Gertler, R., Rosenberg, R., Diepstra, J.H., R?der, C., Nekarda, H., Molnar, B., Tulassay, Z., van Muijen, G.N. and Vogel, I., (2003) Reliability of quantitative reverse-transcriptase-PCR-based detection of tumour cells in the blood between different laboratories using a standardised protocol. European Journal of Cancer, 39, 388-396. doi:10.1016/S0959-8049(02)00631-7

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• TITLE: Behavior of circulating epithelial tumor cells (CETC) and FISH (fluorescence in situ hybridisation) of epidermal growth factor receptor (EGFR)-gene amplification in lung cancer patients during the course of therapy

  AUTHORS: May El Sherif, Claus Peter Schneider, Carola Rabenstein, Amina Hessein Hassab, Magdy Mamdouh El Bordiny, Mona Wagdy Ayad, Katharina Pachmann

  KEYWORDS: Circulating Epithelial Tumor Cells; Lung Cancer; EGFR-Gene Mutation; Amplification; FISH

  JOURNAL NAME: Advances in Lung Cancer, Vol.2 No.1, March 21, 2013

  ABSTRACT: Introduction: Monitoring the response of CETC to therapy in lung cancer allows early detection of patients at risk of progression. Analysis of the EGFR-gene amplification in these cells may help to characterize patients who might benefit from tyrosine kinase inhibitors. Methods: CETCs were quantified at least twice during treatment from blood of 52 patients with advanced non small cell lung cancer (NSCLC) using fluorescence labelled anti-EpCAM. EGFR-gene amplification was analysed in these cells with double probe (EGFR/CEP7) using FISH analysis. Results: Progression of the tumor was observed in 30 of the 52 patients (58%). With respect to changes in CETCs during therapy and progression free survival 31 patients showed a decrease in CETCs, 2 developing a single brain metastasis and 12 progressive disease; 20 patients showed an increase in CETC more than twofold 16 of which developed progressive disease. The difference was highly significant (p=0.007 Fisher’s exact test) irrespective of age, sex, tumor size, pathological type and therapy. Kaplan-Meier progression free survival was significantly different between patients with decreasing and increaseing CETC (p=0.038). 5/20 patients tested were positive for EGFR amplification with 85-100% of EpCAM positive cells showing this chromosomal abnormality. One patient could be followed during therapy with increasing CETC during therapy with bevacizumab followed by relapse. He subsequently received erlotinib resulting in a decrease in CETC and is still free of progress after 516 days. Conclusions: These results show that peripherally circulating tumor cells in patients with advanced NSCLC are influenced by systemic chemotherapy and an increase in spite of therapy is a marker of aggressiveness of the tumor cells. Determination of the EGFR amplification might help to better treat part of these patients.