Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms

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Objective: Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms.

Material and Method: In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay.

Results: Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p<0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T>C (rs3746444) polymorphisms and circulating tumor cell positivity were observed.

Conclusion: The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size.

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10. Lyon: International Agency for Research on Cancer; 2010. Available from:

2. Annual Reports. 1982-2008. National Cancer Registry. New Delhi: Indian Council of Medical Research; 1985-2010. Available from:

3. Asthana S, Chauhan S, Labani S. Breast and cervical cancer risk in India: An update. Indian J Public Health. 2014;58:5-10.

4. Pukazhendhi G, Gluck S. Circulating tumor cells in breast cancer. J Carcinog. 2014;13:8.

5. Yu M, Stott S, Toner M, Maheswaran S, Haber DA. Circulating tumor cells: Approaches to isolation and characterization. J Cell Biol. 2011;192:373-82.

6. Ross JS, Slodkowska EA. Circulating and disseminated tumor cells in the management of breast cancer. Am J Clin Pathol. 2009;132: 237-45.

7. Hong B, Zu Y. Detecting circulating tumor cells: Current challenges and new trends. Theranostics. 2013;3:377-94.

8. Rosai J. Breast. In: Rosai J, editor. Rosai and Ackerman’s surgical pathology. 10th ed. New York: Elsevier; 2011.1660-771.

9. Bansal C, Sharma KL, Misra S, Srivastava AN, Mittal B, Singh US. Common genetic variants in pre-microRNAs and risk of breast cancer in the North Indian population. Ecancermedicalscience. 2014;8:473.

10. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 V1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013. Available from:

11. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781-91.

12. Riethdorf S, Wikman H, Pantel K. Review: Biological relevance of disseminated tumor cells in cancer patients. Int J Cancer. 2008;123:1991-2006.

13. Cruz I, Ciuda J, Cruz JJ, Ramos M, Gomez-Alonso A, Adansa JC, Rodriguez C, Orfao A. Evaluation of multiparameter flow cytometry for the detection of breast cancer tumor cells in blood samples. Am J Clin Pathol. 2005;123:66-74.

14. Hristozova T, Konschak R, Budach V, Tinhofer I. A simple multicolor flow cytometry protocol for detection and molecular characterization of circulating tumor cells in epithelial cancers. Cytometry A. 2012;81:489-95.

15. Lucci A, Hall CS, Lodhi AK, Bhattacharyya A, Anderson AE, Xiao L, Bedrosian I, Kuerer HM, Krishnamurthy S. Circulating tumour cells in non-metastatic breast cancer: A prospective study. Lancet Oncol. 2012;13:688-95.

16. Giordano A, Giuliano M, De Laurentiis M, Arpino G, Jackson S, Handy BC, Ueno NT, Andreopoulou E, Alvarez RH, Valero V, De Placido S, Hortobagyi GN, Reuben JM, Cristofanilli M. Circulating tumor cells in immunohistochemical subtypes of metastatic breast cancer: Lack of prediction in HER2-positive disease treated with targeted therapy. Ann Oncol. 2012;23:1144-50.

17. Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, Handy BC, Ueno NT, Alvarez RH, De Laurentiis M, De Placido S, Valero V, Hortobagyi GN, Reuben JM, Cristofanilli M. Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res. 2011;13:R67.

18. Krishnamurthy S, Cristofanilli M, Singh B, Reuben J, Gao H, Cohen EN, Andreopoulou E, Hall CS, Lodhi A, Jackson S, Lucci A. Detection of minimal residual disease in blood and bone marrow in early stage breast cancer. Cancer. 2010;116:3330-7.

19. Turker I, Uyeturk U, Sonmez OU, Oksuzoglu B, Helvaci K, Arslan UY, Budakoglu B, Alkis N, Aksoy S, Zengin N. Detection of circulating tumor cells in breast cancer patients: Prognostic predictive role. Asian Pac J Cancer Prev. 2013;14:1601-7.

20. Franken B, de Groot MR, Mastboom WJ, Vermes I, van der Palen J, Tibbe AG, Terstappen LW. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res. 2012; 14: 133.

21. Peeters DJ, van Dam PJ, Van den Eynden GG, Rutten A, Wuyts H, Pouillon L, Peeters M, Pauwels P, Van Laere SJ, van Dam PA, Vermeulen PB, Dirix LY. Detection and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes. Br J Cancer. 2014;110:375-83.

22. Rack B, Schindlbeck C, Juckstock J, Andergassen U, Hepp P, Zwingers T, Friedl TW, Lorenz R, Tesch H, Fasching PA, Fehm T, Schneeweiss A, Lichtenegger W, Beckmann MW, Friese K, Pantel K, Janni W; SUCCESS Study Group. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106. pii: dju066.

Turkish Journal of Pathology

The Journal of Federation of Turkish Pathology Societies 

Journal Information

Cite Score 2018: 0.88

SCImago Journal Rank (SJR) 2018: 0.3
Source Normalized Impact per Paper (SNIP) 2018: 0.577


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