Abstract

Circulating tumor cells (CTC) are useful in early detection of colorectal cancer. This study described a newly developed platform, integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44 preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%, which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033). No significant association was found between tumor stage, survival and preoperative CTC number. CTCs were detected in 10 colorectal cancer patients one week after surgery; seven patients with decreased CTC numbers (compared with preoperative CTC number) were free of recurrence; whereas two of the three patients with increased CTC numbers had tumor recurrence. Moreover, CTCs were detected in 34 colorectal cancer patients three months after surgery; patients with CTC<2 at three months after surgery had significantly longer Progression Free Survival than those with CTC>=2 (P=0.019); patients with decreased CTC number (compared with preoperative CTC number) had significantly longer Progression Free Survival than those with increased CTC number (P=0.003). In conclusion, CTCs could be detected in various stages of colorectal cancer using SE-iFISH. Dynamic monitoring of CTC numbers could predict recurrence and prognosis.

Highlights

  • Colorectal cancer (CRC) is the fourth common cause of cancer-related deaths in men and the third in women worldwide [1]

  • Circulating tumor cells (CTC) were detected by SE-immunostaining fluorescence in situ hybridization (iFISH) in 40 of 44 preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%, which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033)

  • CTCs were defined as CK+/CD45-/DAPI+/CEP8 = 2, CK+/CD45-/DAPI+/CEP8 > 2, CK-/CD45-/DAPI+/ CEP8 > 2, whereas CK-/CD45+/DAPI+/CEP8 = 2 was defined as WBC (Figure 1a) [23]

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Summary

Introduction

Colorectal cancer (CRC) is the fourth common cause of cancer-related deaths in men and the third in women worldwide [1]. Assessment of treatment responses usually utilizes biomarkers, such as carcinoembryonic antigen (CEA), endoscopy, or serial computed tomography/ magnetic resonance images [3]. The latter is costly procedure and possesses a risk of radiation overexposure, while CEA sensitivity is relatively low (40-60% at the best) [4,5,6], detection of changed CEA levels was a reliable predictive factor of prognosis and treatment response [7]. The clinical utility of CTC as a marker has been evaluated for both prognosis and prediction of treatment responses in metastatic CRC patients [11]. It is imperative to develop an alternative strategy to effectively identify CTCs

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