Abstract
BackgroundEpithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. However, poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. Here, we report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method.MethodsPaired peripheral blood samples were collected from 43 metastatic lung cancer patients to enumerate CTCs using the CellSearch system according to the manufacturer’s protocol and the MCA system by immunolabeling and cytomorphological analysis. The presence of CTCs was assessed blindly and independently by both systems.ResultsCTCs were detected in 17 of 22 NSCLC patients using the MCA system versus 7 of 22 patients using the CellSearch system. On the other hand, CTCs were detected in 20 of 21 small cell lung cancer (SCLC) patients using the MCA system versus 12 of 21 patients using the CellSearch system. Significantly more CTCs in NSCLC patients were detected by the MCA system (median 13, range 0–291 cells/7.5 mL) than by the CellSearch system (median 0, range 0–37 cells/7.5 ml) demonstrating statistical superiority (p = 0.0015). Statistical significance was not reached in SCLC though the trend favoring the MCA system over the CellSearch system was observed (p = 0.2888). The MCA system also isolated CTC clusters from patients who had been identified as CTC negative using the CellSearch system.ConclusionsThe MCA system has a potential to isolate significantly more CTCs and CTC clusters in advanced lung cancer patients compared to the CellSearch system.
Highlights
Lung cancer is the leading cause of cancer-related death in most industrialized countries
It has been suggested that the low prevalence of circulating tumor cells (CTC) detected in patients with advanced non-small cell lung cancer (NSCLC) using the CellSearch system may be due to the loss of Epithelial cell adhesion molecule (EpCAM) expression [17], indicating that EpCAM-based CTC isolation methods cannot achieve stable and reproducible CTC recovery from all tumor types
From each of the 43 patients who were enrolled, among whom 22 had been diagnosed with NSCLC and 21 with Small cell lung cancer (SCLC), 10–15 mL of blood was collected in EDTA tubes for CTC enumeration by the microcavity array (MCA) system in our laboratory (Shizuoka Cancer Center, Shizuoka, Japan) and 20 mL was collected in CellSave collection tubes for CTC enumeration by the CellSearch system in the laboratory of SRL Inc. (Tokyo, Japan)
Summary
Lung cancer is the leading cause of cancer-related death in most industrialized countries. Epithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. Poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. We report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method
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