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Cancer Lett. 2018 Jan 1;412:99-107. doi: 10.1016/j.canlet.2017.10.004. Epub 2017 Oct 13.

Quantified postsurgical small cell size CTCs and EpCAM+ circulating tumor stem cells with cytogenetic abnormalities in hepatocellular carcinoma patients determine cancer relapse.

Author information

1
Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China.
2
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
3
Center for Hepatobiliary Diseases, PLA General Hospital, Beijing, China.
4
Department of Pathology, Beijing Tsinghua Changgung Hospital (BTCH), Beijing, China.
5
Cytelligen, San Diego, CA, USA.
6
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: lin100@medmail.com.
7
Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China. Electronic address: dongjh_btch@163.com.

Abstract

Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such "uncapturable and invisible" CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45-/CD31-) in patients subjected to surgical resection. Clinical significance of diverse subtypes of CTC was systematically investigated. Existence of small cell size CTCs (≤5 μm of WBCs) with cytogenetic abnormality of aneuploid chromosome 8, which constituted majority of the detected CTCs in HCC patients, was demonstrated for the first time. The stemness marker EpCAM+ aneuploid circulating tumor stem cells (CTSCs), and EpCAM- small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity of small triploid CTCs (≥5 cells/6 ml blood), multiploid (≥pentasomy 8) CTSCs or CTM (either one ≥ 1) significantly correlated to HCC patients' poor prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs in post-operative patients help predict neoplasm recurrence.

KEYWORDS:

Aneuploid CTC and circulating tumor stem cell; Hepatobiliary malignancy; Hepatocellular and cholangiocarcinoma; Surgical resection; iFISH

PMID:
29031565
DOI:
10.1016/j.canlet.2017.10.004
[Indexed for MEDLINE]
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