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Int. J. Mol. Sci. 2017, 18(4), 622; doi:10.3390/ijms18040622

Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer

Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editors: Srikumar Chellappan and Jaya Padmanabhan
Received: 16 January 2017 / Revised: 5 March 2017 / Accepted: 7 March 2017 / Published: 23 March 2017
(This article belongs to the Special Issue Pancreatic Disorders)
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Abstract

Pancreatic cancer (PC) is the most lethal type of gastrointestinal cancer, and early detection and monitoring is an urgent problem. Circulating tumor cells (CTCs) are emerging as a non-invasive biomarker for tumor detection. However, the low sensitivity is a main problem in the traditional CellSearch System for detecting CTCs, especially in patients with PC. In this study, we used negative enrichment (NE), immunofluorescence and in situ hybridization (FISH) of chromosome 8 (NE-iFISH) to capture and identify CTCs in PC patients. We showed that the NE-iFISH system exhibited a dramatically high detection rate of CTCs in PC patients (90%). The diagnostic rate of PC reached 97.5% when combining CTCs ≥ 2 and carbohydrate antigen 19-9 (CA19-9) > 37 µmol/L. The 1-year survival in the group of CTCs < 3 was significantly higher than that of CTCs ≥ 3 (p = 0.043). In addition, we analyzed the role of chromosomal instability in CTCs detection. The group of triploid (three hybridization signals of chromosome 8) CTCs ≥ 3 showed a shorter 1-year survival (p = 0.0279) and overall survival (p = 0.0188) than the group with triploid CTCs < 3. Importantly, the triploid CTC number but not the overall CTC counts could be a predictor of chemo-sensitivity. Moreover, circulating tumor microembolus (CTMs) were found in stage IV patients, and were positively related to the poor response to chemotherapy. In conclusion, the NE-iFISH system significantly improved the positive detection rate of CTCs and triploid CTC could be used to predict prognosis or the response to the chemotherapy of PC patients. CTM is a potential indicator of the chemotherapeutic effect in advanced PC patients. View Full-Text
Keywords: triploid; circulating tumor microembolus; NE-iFISH; pancreatic cancer triploid; circulating tumor microembolus; NE-iFISH; pancreatic cancer
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MDPI and ACS Style

Xu, Y.; Qin, T.; Li, J.; Wang, X.; Gao, C.; Xu, C.; Hao, J.; Liu, J.; Gao, S.; Ren, H. Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer. Int. J. Mol. Sci. 2017, 18, 622.

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