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

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

Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Departement of Experimental Heamatology and Oncology, Clinic for Internal Medicine II Friedrich-Schiller-Universit?t Jena, Jena, Germany.
Oncology Departement Bad Berka Central Clinic, Bad Berka, Germany.
Transfusion Center Bayreuth, Bayreuth, Germany.

DOI: 10.4236/alc.2013.21001                

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.

Keywords

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

Conflicts of Interest

The authors declare no conflicts of interest.

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