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DIsseminated tumor cells of luminal breast cancer patients .

https://doi.org/10.17650/1726-9784-2018-17-1-53-57

Abstract

Introduction. There is ample evidence that disseminated tumor cells (DTC), which are found in the bone marrow (BM) of patients with breast cancer (BC), including early stages, are progenitors of subsequent distant metastasis. Therefore, BM-DTC represent an additional tool for understanding carcinogenesis and estimating prognosis. Nevertheless, the existing data are controversial. The purpose of the study – to determine the frequency of DTC detection in BM of patients with luminal BC and also its relationship with some clinical and immunophenotypic parameters. Materials and methods. BM bioptates of 65 luminal BC patients were analyzed for the presence of DTC by Attune Acoustic Focusing Cytometer. For the first time in Russia, the sensitivity of the DTC detection method in the BM to the level of 1 × 10–7 myelocaryocytes was increased. Results. In BM, DTC were detected in 40 % of patients, and this finding did not correlate with stage of BC and degree of malignancy. The level of CD8+ lymphocytes in patients with DTC in the BM was significantly lower and amounted to 39,2 % versus 48,1 % in patients without DTC (p = 0,011). The content of myelocaryocytes with DTC-positive status was 1,6 times lower than in the absence of DTC (р = 0,007). Other parameters of the myelogram did not differ significantly. Moreover, no significant correlations were found between the presence of DTC in BM and the breast tumor immunophenotype (HLA-I: p = 0,74; HLA-DR: p = 0,93; CD71: p = 0,46). Conclusion. The presence of BM-DTC is more interrelated with myelogram and subpopulation of BM lymphocytes than with the clinical characteristics of tumor.

About the Authors

D. A. Ryabchikov
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


O. A. Beznos
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


I. A. Dudina
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)
Russian Federation
Build. 2, 8 Trubetskaya St., Moscow 119991


I. K. Vorotnikov
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


D. A. Denchik
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


S. V. Chulkova
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


O. A. Talipov
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


N. N. Tupitsyn
N.N. Blokhin National Medical Research Center of Oncology , Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


References

1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005;365:1687–717. DOI: 10.1016/S0140-6736(05)66544-0.

2. Воротников И.К., Чхиквадзе Н.В., Рябчиков Д.А. и др. Лимфаденэктомия при раке молочной железы: за и против. Злокачественные опухоли 2016;(2):37–42. DOI: 10.18027/2224-5057-2016-2-37-42.

3. Hartkopf A.D., Wallwiener M., Hahn M. et al. Simultaneous Detection of Disseminated and Circulating Tumor Cells in Primary Breast Cancer Patients. Cancer Res Treat 2016;48(1):115–24. DOI: 10.4143/crt.2014.287.

4. Braun S., Vogl F.D., Naume B. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005;353:793–802. DOI: 10.1056/NEJMoa050434.

5. Beznos O.A., Artamonova E.V., Tupitsyn N.N. Disseminated tumor cell subpopulations: approaches to identification and clinical significance. Haematopoiesis Immunology 2016; 14(1):73–9.

6. Uhr J.W., Pantel K. Controversies in clinical cancer dormancy. Proc Natl Acad Sci USA 2011;108:12396–400. DOI: 10.1073/pnas.1106613108.

7. Chambers A.F., Groom A.C., MacDonald I.C. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002;2:563–72. DOI: 10.1038/nrc865.

8. Давыдов М.И., Тупицын Н.Н., Григорьева Т.А. и др. Метод проточной цитометрии в оценке минимального поражения костного мозга у больных раком. Иммунология гемопоэза 2014;12(1):8–17.

9. Wölfle U., Müller V., Pantel K. Disseminated tumor cells in breast cancer: detection, characterization and clinical relevance. Future Oncol 2006; 2(4):553–61. DOI: 10.2217/14796694.2.4.553.

10. Funke I., Schraut W. Meta-analyses of studies on bone marrow micrometastasis: an independent prognostic impact remains to be substantiated. J Clin Oncol 1998;16(2):557–66. DOI: 10.1200/JCO.1998.16.2.557.

11. Крохина О.В., Летягин В.П., Тупицын Н.Н. и др. Иммуноморфологическая диагностика микрометастазов рака молочной железы в костный мозг. Опухоли женской репродуктивной системы 2005;(1):70–3.

12. Molino A., Pelosi G., Turazza M. et al. Bone marrow micrometastases in 109 breast cancer patients: correlations with clinical and pathological features and prognosis. Breast Cancer Res Treat 1997;42:23–30. PMID: 9116315.

13. Артамонова Е.В. Роль иммунофенотипирования опухолевых клеток в диагностике и прогнозе рака молочной железы. Автореф. дис. … д-ра мед. наук. М., 2003.

14. Pages F., Galon J., Dieu-Nosjean M.C. et al. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 2010;29:1093–102. DOI: 10.1038/onc.2009.416.

15. Capietto A.-H., Faccio R. Immune regulation of bone metastasis. Bonekey Rep 2014;3:600. DOI: 10.1038/bonekey.2014.95.

16. Григорьева Т.А., Безнос О.А., Тупицын Н.Н. Субпопуляции лимфоцитов костного мозга больных раком молочной железы. Опухоли женской репродуктивной системы 2015;(2): 52–5. DOI: 10.17650/1994-4098-2015-11-2-52-55.

17. Biylgi O., Karagöz B., Türken O. et al. CD4+CD25 high, CD8CD28– cells and thyroid autoantibodies in breast cancer patients. Cent Eur J Immunol 2014;39(3):338–44. DOI: 10.5114/ceji.2014.45945.

18. Bedri S., Mohamed M., Sarwath H., Sastry K. Characterization and quantification of tumor infiltrating lymphocytes in breast cancer. J Immunother Cancer 2014;2(Suppl 1):P9. DOI: 10.1186/2051-1426-2-S1-P9.

19. Rathore A.S., Kumar S., Konwar R. et al. An Indian CD3+, CD4 & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast. J Med Res 2014;140(3):361–9. PMCID: PMC4248382.

20. Ellinidi V.N., Anikeeva N.V., Goncharova O.A., Krasnozhon D.A. Natural killer cells (CD56, CD16) as a factor of local antitumor immunity in breast cancer. Voprosy onkologii 2005;51(4):447–9. PMID: 16308976.

21. Kaneko K., Ishigami S., Kijima Y. et al. BMC Clinical implication of HLA class I expression in breast cancer. Cancer 2011;11:454. DOI: 10.1186/1471-2407-11-454.


Review

For citations:


Ryabchikov D.A., Beznos O.A., Dudina I.A., Vorotnikov I.K., Denchik D.A., Chulkova S.V., Talipov O.A., Tupitsyn N.N. DIsseminated tumor cells of luminal breast cancer patients . Russian Journal of Biotherapy. 2018;17(1):53-57. (In Russ.) https://doi.org/10.17650/1726-9784-2018-17-1-53-57

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