Circulating Tumor Cells Allow Early Diagnosis of Lung Cancer

Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer and migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis.

The overall prognosis of lung cancer remains dismal, in particular at advanced stages of non-small-cell lung cancer (NSCLC) patients and one of the reasons for the poor prognosis in NSCLC patients is the absence of routine, easy to perform and low cost methods that allow detection of asymptomatic early-stage tumors.

Scientists at the Pasteur Hospital, (Nice, France) enrolled in a prospective study 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), which included 42 control smokers and 35 non-smoking healthy individuals, between June 2008 and April 2012. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers.

CTC detection was performed using The Isolation by Size of Epithelial Tumor cells (ISET) technology (Rarecells Diagnostics; Paris, France). The ISET method is a blood filtration-based approach, which enriches on a polycarbonate membrane cells larger than eight micrometers. The membrane was processed both for immunocytochemistry and for May Grünwald Giemsa (MGG) staining for cytological analysis. Immunocytochemistry was performed using double immunolabeling. Using ISET, patients were considered positive for CTCs based on cytopathological analysis of the isolated cells and detection of cells with characteristic malignant features determined according to previously defined criteria.

CTCs were detected in 5 of the 168 patients (3%) of COPD patients. Isolated cells with benign cytomorphological features were detected by ISET in 3 out of 168 patients (1.8%) of COPD patients. None of these three patients and none of the other 160 patients with COPD, and with no pathological cells at baseline in the blood, were shown to develop a lung nodule, as demonstrated by a yearly computerized tomography (CT)-scan during the subsequent follow-up starting with the first blood filtration.

The authors concluded that a sensitive and diagnostic CTC detection approach can find CTCs in patients “at risk” of developing lung cancer without a detectable nodule by CT scan. A small fraction of COPD patients were found to have CTCs one to four years before identification of a lung nodule by imaging. In five patients, the lung cancer was diagnosed at an early stage (IA) allowing prompt surgical resection; they were then shown to be without tumor recurrence and without CTCs 16 months after surgery. The study was published on October 31, 2014, in the journal Public Library of Science ONE.

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