Evaluation of Circulating Tumor Cells in Colorectal Cancer Using Flow Cytometry

Overview

Journal J Int Med Res

Publisher Sage Publications

Specialty General Medicine

Date 2021 Sep 30

PMID 34587798

Citations 4

Authors

Ana-Maria Musina

Mihaela Zlei

Mihaela Mentel

Dragos-Viorel Scripcariu

Madalina Stefan

Maria-Gabriela Anitei

Bogdan Filip

Iulian Radu

Mihaela-Madalina Gavrilescu

Andrian Panuta

Mihaela Buna-Arvinte

Cristiana-Ioana Cordun

Dragos-Valentin Predescu

Viorel Scripcariu

Ionut Hutanu

Affiliations

Soon will be listed here.

Abstract

Objective: We aimed to evaluate the prognostic value of circulating tumor cells (CTCs) and the impact of intraoperative tumor manipulation on CTCs in colorectal cancer (CRC) patients.

Methods: We performed a prospective study on 40 patients with CRC stages I to IV who received curative surgery using the no-touch technique. Flow cytometry was used to identify CTCs in peripheral blood samples (4 mL/sample) collected at two surgical moments: skin incision (T1) and after surgical resection (T2). A threshold of ≥4 CTCs/4 mL blood was established for considering patients CTC positive.

Results: In the univariate analysis, CTC evaluation at T2 was correlated with female sex, vascular invasion, tumor localization in the colon and metastatic lymph nodes. In the multivariate analysis, only female sex and colon cancer maintained statistical significance. At a medium follow-up of 15 months (1-25 months), the mortality rate was 10% (n = 4), with no significant differences between the overall survival of T1 or T2 CTC-positive and CTC-negative patients.

Conclusions: Flow cytometry is a feasible CTC identification technique in CRC, and although surgical manipulation has no influence on CTC numbers, CTCs may serve as a prognostic and predictive factor.

Citing Articles

Nanozyme-based aptasensors for the detection of tumor biomarkers.

Wang K, Lin X, Lv X, Xie M, Wu J, Wu J J Biol Eng. 2025; 19(1):13.

PMID: 39920818 PMC: 11806818. DOI: 10.1186/s13036-025-00485-0.

Circulating tumor cells in colorectal cancer - a review of detection methods and clinical relevance.

Saadi S, Aarab M, Tabyaoui I, Tahiri Jouti N Contemp Oncol (Pozn). 2024; 27(3):123-131.

PMID: 38239860 PMC: 10793619. DOI: 10.5114/wo.2023.133740.

Assessing Tumorigenicity in Stem Cell-Derived Therapeutic Products: A Critical Step in Safeguarding Regenerative Medicine.

Wang Z Bioengineering (Basel). 2023; 10(7).

PMID: 37508884 PMC: 10376867. DOI: 10.3390/bioengineering10070857.

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis.

Wu Y, Li W, Chen X, Wang H, Su S, Xu Y Front Immunol. 2023; 14:1051506.

PMID: 36776873 PMC: 9909470. DOI: 10.3389/fimmu.2023.1051506.

Detection and Characterization of Circulating Tumor Cells Using Imaging Flow Cytometry-A Perspective Study.

Muchlinska A, Smentoch J, Zaczek A, Bednarz-Knoll N Cancers (Basel). 2022; 14(17).

PMID: 36077716 PMC: 9454939. DOI: 10.3390/cancers14174178.

References

Duda D, Cohen K, Scadden D, Jain R . A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood. Nat Protoc. 2007; 2(4):805-10. PMC: 2686125. DOI: 10.1038/nprot.2007.111. View

Cohen S, Alpaugh R, Gross S, OHara S, Smirnov D, Terstappen L . Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2006; 6(2):125-32. DOI: 10.3816/CCC.2006.n.029. View

Lampignano R, Schneck H, Neumann M, Fehm T, Neubauer H . Enrichment, Isolation and Molecular Characterization of EpCAM-Negative Circulating Tumor Cells. Adv Exp Med Biol. 2017; 994:181-203. DOI: 10.1007/978-3-319-55947-6_10. View

Peach G, Kim C, Zacharakis E, Purkayastha S, Ziprin P . Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer. 2010; 102(9):1327-34. PMC: 2865760. DOI: 10.1038/sj.bjc.6605651. View

Bahnassy A, Salem S, Mohanad M, Abulezz N, Abdellateif M, Hussein M . Prognostic significance of circulating tumor cells (CTCs) in Egyptian non-metastatic colorectal cancer patients: A comparative study for four different techniques of detection (Flowcytometry, CellSearch, Quantitative Real-time PCR and Cytomorphology). Exp Mol Pathol. 2018; 106:90-101. DOI: 10.1016/j.yexmp.2018.12.006. View

Fang C, Fan C, Wang C, Huang Q, Meng W, Yu Y . Prognostic value of CD133 CD54 CD44 circulating tumor cells in colorectal cancer with liver metastasis. Cancer Med. 2017; 6(12):2850-2857. PMC: 5727299. DOI: 10.1002/cam4.1241. View

Rothe F, Maetens M, Rouas G, Paesmans M, Van den Eynde M, Van Laethem J . CTCs as a prognostic and predictive biomarker for stage II/III Colon Cancer: a companion study to the PePiTA trial. BMC Cancer. 2019; 19(1):304. PMC: 6446374. DOI: 10.1186/s12885-019-5528-1. View

Tralhao J, Hoti E, Serodio M, Laranjeiro P, Paiva A, Abrantes A . Perioperative tumor cell dissemination in patients with primary or metastatic colorectal cancer. Eur J Surg Oncol. 2009; 36(2):125-9. DOI: 10.1016/j.ejso.2009.07.003. View

Bidard F, Kiavue N, Ychou M, Cabel L, Stern M, Madic J . Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial. Cells. 2019; 8(6). PMC: 6627974. DOI: 10.3390/cells8060516. View

10.

Katsuno H, Zacharakis E, Aziz O, Rao C, Deeba S, Paraskeva P . Does the presence of circulating tumor cells in the venous drainage of curative colorectal cancer resections determine prognosis? A meta-analysis. Ann Surg Oncol. 2008; 15(11):3083-91. DOI: 10.1245/s10434-008-0131-8. View

11.

Lu Y, Liang H, Yu T, Xie J, Chen S, Dong H . Isolation and characterization of living circulating tumor cells in patients by immunomagnetic negative enrichment coupled with flow cytometry. Cancer. 2015; 121(17):3036-45. DOI: 10.1002/cncr.29444. View

12.

Mavroudis D . Circulating cancer cells. Ann Oncol. 2010; 21 Suppl 7:vii95-100. DOI: 10.1093/annonc/mdq378. View

13.

Baek D, Kim G, Song G, Han I, Park E, Kim H . Clinical Potential of Circulating Tumor Cells in Colorectal Cancer: A Prospective Study. Clin Transl Gastroenterol. 2019; 10(7):e00055. PMC: 6708664. DOI: 10.14309/ctg.0000000000000055. View

14.

Scripcariu V, Scripcariu D, Filip B, Gavrilescu M, Musina A, Volovat C . "Liquid Biopsy" - Is it a Feasible Option in Colorectal Cancer?. Chirurgia (Bucur). 2019; 114(2):162-166. DOI: 10.21614/chirurgia.114.2.162. View

15.

Tsavellas G, Huang A, McCullough T, Patel H, Araia R, Allen-Mersh T . Flow cytometry correlates with RT-PCR for detection of spiked but not circulating colorectal cancer cells. Clin Exp Metastasis. 2002; 19(6):495-502. DOI: 10.1023/a:1020350117292. View

16.

Lu Y, Wang P, Peng J, Wang X, Zhu Y, Shen N . Meta-analysis Reveals the Prognostic Value of Circulating Tumour Cells Detected in the Peripheral Blood in Patients with Non-Metastatic Colorectal Cancer. Sci Rep. 2017; 7(1):905. PMC: 5430457. DOI: 10.1038/s41598-017-01066-y. View

17.

Vacante M, Ciuni R, Basile F, Biondi A . The Liquid Biopsy in the Management of Colorectal Cancer: An Overview. Biomedicines. 2020; 8(9). PMC: 7555636. DOI: 10.3390/biomedicines8090308. View

18.

Wang L, Zhou S, Zhang W, Wang J, Wang M, Hu X . Circulating tumor cells as an independent prognostic factor in advanced colorectal cancer: a retrospective study in 121 patients. Int J Colorectal Dis. 2019; 34(4):589-597. DOI: 10.1007/s00384-018-03223-9. View

19.

Galizia G, Gemei M, Orditura M, Romano C, Zamboli A, Castellano P . Postoperative detection of circulating tumor cells predicts tumor recurrence in colorectal cancer patients. J Gastrointest Surg. 2013; 17(10):1809-18. DOI: 10.1007/s11605-013-2258-6. View

20.

Koyanagi K, Bilchik A, Saha S, Turner R, Wiese D, McCarter M . Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial. Clin Cancer Res. 2008; 14(22):7391-6. PMC: 2586882. DOI: 10.1158/1078-0432.CCR-08-0290. View