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2 "Circulating neoplastic cells"
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A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer
Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park
Cancer Res Treat. 2016;48(4):1229-1242.   Published online March 30, 2016
DOI: https://doi.org/10.4143/crt.2015.500
AbstractAbstract PDFPubReaderePub
Purpose
We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis.
Materials and Methods
Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1.
Results
The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients.
Conclusion
This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC.

Citations

Citations to this article as recorded by  
  • Hydrogel-based technologies in liquid biopsy for the detection of circulating clinical markers: challenges and prospects
    Young Jun Kim, Junhong Min
    Analytical and Bioanalytical Chemistry.2024; 416(9): 2065.     CrossRef
  • Diagnostic value of expressions of cancer stem cell markers for adverse outcomes of hepatocellular carcinoma and their associations with prognosis: A Bayesian network meta‑analysis
    Zhengrong Ou, Shoushuo Fu, Jian Yi, Jingxuan Huang, Weidong Zhu
    Oncology Letters.2024;[Epub]     CrossRef
  • Finding the seed of recurrence: Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment
    Francesca Carissimi, Matteo Nazzareno Barbaglia, Livia Salmi, Cristina Ciulli, Linda Roccamatisi, Giuseppe Cordaro, Venkata Ramana Mallela, Rosalba Minisini, Biagio Eugenio Leone, Matteo Donadon, Guido Torzilli, Mario Pirisi, Fabrizio Romano, Simone Famul
    World Journal of Gastrointestinal Surgery.2021; 13(9): 967.     CrossRef
  • Fabrication of Formalin-Fixed, Paraffin-Embedded (FFPE) Circulating Tumor Cell (CTC) Block Using a Hydrogel Core-Mediated Method
    Tae Hee Lee, Young Jun Kim, Woo Sun Rou, Hyuk Soo Eun
    Micromachines.2021; 12(9): 1128.     CrossRef
  • Isolation and morphology of circulating tumor cells by cell block technique in breast cancer
    Nandini Agrawal, Rajpal S. Punia, Uma Handa, Ashok K. Attri
    Indian Journal of Pathology and Microbiology.2021; 64(2): 329.     CrossRef
  • Circulating tumor cells in the clinical cancer diagnosis
    P. Zhang, H. Zhou, K. Lu, Y. Wang, T. Feng
    Clinical and Translational Oncology.2020; 22(3): 279.     CrossRef
  • A microfluidic system based on the monoclonal antibody BCMab1 specifically captures circulating tumor cells from bladder cancer patients
    Yunchao Wang, Qing Liu, Tongyi Men, Ye Liang, Haitao Niu, Jianning Wang
    Journal of Biomaterials Science, Polymer Edition.2020; 31(9): 1199.     CrossRef
  • The Significance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma: Real-Time Monitoring and Moving Targets for Cancer Therapy
    Feiyu Chen, Zhangfeng Zhong, Hor-Yue Tan, Ning Wang, Yibin Feng
    Cancers.2020; 12(7): 1734.     CrossRef
  • The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis
    Theresa D. Ahrens, Sara R. Bang-Christensen, Amalie M. Jørgensen, Caroline Løppke, Charlotte B. Spliid, Nicolai T. Sand, Thomas M. Clausen, Ali Salanti, Mette Ø. Agerbæk
    Frontiers in Cell and Developmental Biology.2020;[Epub]     CrossRef
  • Efficient Detection and Single-Cell Extraction of Circulating Tumor Cells in Peripheral Blood
    Rui Li, Zhiyi Gong, Kezhen Yi, Wei Li, Yichao Liu, Fubing Wang, Shi-shang Guo
    ACS Applied Bio Materials.2020; 3(9): 6521.     CrossRef
  • Downregulation of cytokeratin 18 induces cellular partial EMT and stemness through increasing EpCAM expression in breast cancer
    Ruizan Shi, Linhong Liu, Fengge Wang, Yifan He, Yanan Niu, Chang Wang, Xuanping Zhang, Xiuli Zhang, Huifeng Zhang, Min Chen, Yan Wang
    Cellular Signalling.2020; 76: 109810.     CrossRef
  • Cell blocks in cytopathology: An update
    Aruna Nambirajan, Deepali Jain
    Cytopathology.2018; 29(6): 505.     CrossRef
  • Cytopathological Study of the Circulating Tumor Cells filtered from the Cancer Patients’ Blood using Hydrogel-based Cell Block Formation
    Yoon-Tae Kang, Young Jun Kim, Tae Hee Lee, Young-Ho Cho, Hee Jin Chang, Hyun-Moo Lee
    Scientific Reports.2018;[Epub]     CrossRef
  • Dual-patterned immunofiltration (DIF) device for the rapid efficient negative selection of heterogeneous circulating tumor cells
    Jiyoon Bu, Yoon-Tae Kang, Young Jun Kim, Young-Ho Cho, Hee Jin Chang, Hojoong Kim, Byung-In Moon, Ho Gak Kim
    Lab on a Chip.2016; 16(24): 4759.     CrossRef
  • 15,885 View
  • 306 Download
  • 17 Web of Science
  • 14 Crossref
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Simultaneous Detection of Disseminated and Circulating Tumor Cells in Primary Breast Cancer Patients
Andreas D. Hartkopf, Markus Wallwiener, Markus Hahn, Tanja N. Fehm, Sara Y. Brucker, Florin-Andrei Taran
Cancer Res Treat. 2016;48(1):115-124.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.287
AbstractAbstract PDFPubReaderePub
Purpose
Disseminated tumor cells (DTCs) from bone marrow (BM) are a surrogate of minimal residual disease (MRD) in primary breast cancer (PBC) patients and associated with an adverse prognosis. However, BM sampling is an invasive procedure. Although there is growing evidence that circulating tumor cells (CTCs) from the blood are also suitable for monitoring MRD, data on the simultaneous detection of DTCs and CTCs are limited. Materials and Methods We determined the presence of DTCs using immunocytochemistry and the pan-cytokeratin antibody A45-B/B3. CTCs were determined simultaneously using a reverse transcriptionpolymerase chain reaction–based assay (AdnaTest Breast Cancer) and CellSearch (at least one CTC per 7.5 mL blood). We compared the detection of DTCs and CTCs and evaluated their impact on disease-free and overall survival.
Results
Of 585 patients, 131 (22%) were positive for DTCs; 19 of 202 (9%) and 18 of 383 (5%) patients were positive for CTCs, as shown by AdnaTest and CellSearch, respectively. No significant association was observed between DTCs and CTCs (p=0.248 and p=0.146 as shown by AdnaTest and CellSearch, respectively). The presence of DTCs (p=0.046) and the presence of CTCs as shown by CellSearch (p=0.007) were predictive of disease-free survival. Conclusion Our data confirm the prognostic relevance of DTCs and CTCs in patients with PBC. As we found no significant relationship between DTCs and CTCs, prospective trials should include their simultaneous detection. Within those trials, the question of whether or not DTCs and CTCs are independent subpopulations of malignant cell clones should be determined by molecular characterization.

Citations

Citations to this article as recorded by  
  • A comprehensive review and meta-analysis of CTC isolation methods in breast cancer
    Alexey S. Rzhevskiy, Guzel R. Sagitova, Tamilla A. Karashaeva, Andrey O. Morozov, Anastasia S. Fatyanova, Vlada V. Kazantseva, Simon A. Joosse, Andrei V. Zvyagin, Majid Ebrahimi Warkini
    Critical Reviews in Oncology/Hematology.2025; 206: 104579.     CrossRef
  • High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer
    Andy Göbel, Tilman D. Rachner, Oliver Hoffmann, Daniel Martin Klotz, Sabine Kasimir-Bauer, Rainer Kimmig, Lorenz C. Hofbauer, Ann-Kathrin Bittner
    Archives of Gynecology and Obstetrics.2024; 309(6): 2789.     CrossRef
  • Circulating tumor cells in early lobular versus ductal breast cancer and their associations with prognosis
    Silver Alkhafaji, Denise M. Wolf, Mark Jesus M. Magbanua, Laura J. van ‘t Veer, John W. Park, Laura Esserman, Rita A. Mukhtar
    npj Breast Cancer.2024;[Epub]     CrossRef
  • Correlation between Imaging Markers Derived from PET/MRI and Invasive Acquired Biomarkers in Newly Diagnosed Breast Cancer
    Kai Jannusch, Ann-Kathrin Bittner, Nils Martin Bruckmann, Janna Morawitz, Cleo Stieglitz, Frederic Dietzel, Harald H. Quick, Hideo A. Baba, Ken Herrmann, Lale Umutlu, Gerald Antoch, Julian Kirchner, Sabine Kasimir-Bauer, Oliver Hoffmann
    Cancers.2023; 15(6): 1651.     CrossRef
  • The Role of Circulating Tumor Cells in Breast Cancer and Implications for Radiation Treatment Decisions
    Chelain R. Goodman, Corey W. Speers
    International Journal of Radiation Oncology*Biology*Physics.2021; 109(1): 44.     CrossRef
  • Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis
    Andreas D. Hartkopf, Sara Y. Brucker, Florin-Andrei Taran, Nadia Harbeck, Alexandra von Au, Bjørn Naume, Jean-Yves Pierga, Oliver Hoffmann, Matthias W. Beckmann, Lisa Rydén, Tanja Fehm, Rebecca Aft, Montserrat Solà, Vincent Walter, Brigitte Rack, Florian
    European Journal of Cancer.2021; 154: 128.     CrossRef
  • The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance
    Hassan Dianat-Moghadam, Mehdi Azizi, Zahra Eslami-S, Luis Enrique Cortés-Hernández, Maryam Heidarifard, Mohammad Nouri, Catherine Alix-Panabières
    Cancers.2020; 12(4): 867.     CrossRef
  • The biology and clinical potential of circulating tumor cells
    Taja Lozar, Klara Gersak, Maja Cemazar, Cvetka Grasic Kuhar, Tanja Jesenko
    Radiology and Oncology.2019; 53(2): 131.     CrossRef
  • The Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer Prior to any Systematic Therapy: A Systematic Review
    Sepideh Mansouri, Parisa Mokhtari-Hesari, Fatemeh Naghavi-al-Hosseini, Keivan Majidzadeh-A, Leila Farahmand
    Current Stem Cell Research & Therapy.2019; 14(6): 519.     CrossRef
  • Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer
    Mark Jesus M. Magbanua, Christina Yau, Denise M. Wolf, Jin Sun Lee, Aheli Chattopadhyay, Janet H. Scott, Erin Bowlby-Yoder, E. Shelley Hwang, Michael Alvarado, Cheryl A. Ewing, Amy L. Delson, Laura J. van't Veer, Laura Esserman, John W. Park
    Clinical Cancer Research.2019; 25(17): 5388.     CrossRef
  • Simultaneous detection of circulating and disseminated tumor cells in primary breast cancer patients following neoadjuvant chemotherapy
    Vincent P. Walter, Florin-Andrei Taran, Markus Wallwiener, Markus Hahn, Sara Y. Brucker, Andreas D. Hartkopf
    Archives of Gynecology and Obstetrics.2018; 297(3): 785.     CrossRef
  • Clinical applications of the CellSearch platform in cancer patients
    Sabine Riethdorf, Linda O'Flaherty, Claudia Hille, Klaus Pantel
    Advanced Drug Delivery Reviews.2018; 125: 102.     CrossRef
  • DIsseminated tumor cells of luminal breast cancer patients .
    D. A. Ryabchikov, O. A. Beznos, I. A. Dudina, I. K. Vorotnikov, D. A. Denchik, S. V. Chulkova, O. A. Talipov, N. N. Tupitsyn
    Russian Journal of Biotherapy.2018; 17(1): 53.     CrossRef
  • Enrichment and Molecular Analysis of Breast Cancer Disseminated Tumor Cells from Bone Marrow Using Microfiltration
    Sreeraj G. Pillai, Peixuan Zhu, Chidananda M. Siddappa, Daniel L. Adams, Shuhong Li, Olga V. Makarova, Pete Amstutz, Ryan Nunley, Cha-Mei Tang, Mark A. Watson, Rebecca L. Aft, Harriet Wikman
    PLOS ONE.2017; 12(1): e0170761.     CrossRef
  • Clinical and biological significance of circulating tumor cells in cancer
    Takaaki Masuda, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori
    Molecular Oncology.2016; 10(3): 408.     CrossRef
  • Seroma Cytology in Breast Cancer: An Underappreciated Issue
    Huseyin Ozgur Aytac, Tarik Zafer Nursal, Tamer Çolakoğlu, Filiz Aka Bolat, Gökhan Moray
    Clinical Breast Cancer.2016; 16(6): e187.     CrossRef
  • Detection and prevalence of disseminated tumor cells from the bone marrow of early stage male breast cancer patients
    Andreas D. Hartkopf, Florin-Andrei Taran, Christina B. Walter, Markus Hahn, Tanja Fehm, Markus Wallwiener, Sara Y. Brucker
    Breast Cancer Research and Treatment.2015; 152(1): 51.     CrossRef
  • Expression of truncated human epidermal growth factor receptor 2 on circulating tumor cells of breast cancer patients
    Galatea Kallergi, Sofia Agelaki, Maria A. Papadaki, Dimitris Nasias, Alexios Matikas, Dimitris Mavroudis, Vassilis Georgoulias
    Breast Cancer Research.2015;[Epub]     CrossRef
  • 15,325 View
  • 86 Download
  • 18 Web of Science
  • 18 Crossref
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