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.