Novosti
Khirurgii
This journal is
indexed in Scopus









Year 2018 Vol. 26 No 4

ONCOLOGY

DOI: https://dx.doi.org/10.18484/2305-0047.2018.4.457   |  

YA. A. SHLIAKHTUNOU

CLINICAL IMPORTANCE OF EXPRESSION OF BIRC5 AND HER2-NEU GENES IN CIRCULATING TUMOR CELLS AS MARKERS OF MINIMUM RESIDUAL DISEASE IN SURGICAL TREATMENT OF BREAST CANCER

Vitebsk State Medical University, Vitebsk,
The Republic of Belarus

Objective. To evaluate the clinical significance of the expression of BIRC5 and HER2-neu genes in circulating tumor cells as markers of minimal residual disease at the stage of surgical treatment of breast cancer.
Methods. 162 patients with the verified breast cancer of the IIIIC stage aged 58.169.98 years took part in the study. All women underwent surgery in the amount of a Madden radical mastectomy 113 (69.8%) or radical resection 49 (30.2%). All patients on the day of surgery and also on the 2nd day after the operation were examined for the presence of circulating tumor cells (CTCs) in the peripheral blood. For the identification of CTCs, expression of the BIRC5 and HER2-neu genes was studied using real-time polymerase chain reaction (RT-PCR).
Results. Positive mRNAs BIRC5 and HER2-neu CTCs before the surgery were detected in 115 women (71%). After the operation, CTCs disappeared in 47 (40.9%) patients, in 59 (51.3%) CTCs were preserved, and in 9 (7.8%) CTCs were first identified in the venous blood. After mastectomy the frequency of preservation of CTCs was significantly lower than after radical resection and was 46.9% compared to 61.8% (p=0.039). The frequency of preservation of CTCs after surgery was significantly higher in the early stages (IIIA) 66.2% than in more advanced stages (IIBIIIC) 45.0%.
Conclusions. Determination of the expression of the BIRC5 and HER2-neu gene in the enriched peripheral blood sample is a reliable identifier of the CTCs and the minimal residual disease marker. Early dissemination of tumor cells helps maintain CTCs in the peripheral blood of patients to 51.3%, despite the surgical intervention.

Keywords: breast cancer, minimal residual disease, circulating tumor cells, survivin, epidermal growth factor receptor
p. 457-464 of the original issue
References
  1. Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S, Cardoso F. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. ESMO Guidelines Committee. Ann Oncol. 2015;26 (5):v8-30. doi: 10.1093/annonc/mdv298
  2. Cheng L, Swartz MD, Zhao H, Kapadia AS, Lai D, Rowan PJ, Buchholz TA, Giordano SH (2012) Hazard of recurrence among women after primary breast cancer treatmenta 10-year follow- up using data from SEER-Medicare. Cancer Epidemiol Biomark Prev. 2012; 21(5):800-809. doi: 10.1158/1055-9965.EPI-11-1089
  3. Pantel K, Alix-Panabières C, Riethdorf. Cancer micrometastases. Nature Reviews Clinical Oncology. 2009;6(6): 33951. doi: 10.1038/nrclinonc.2009.44.
  4. Onstenk W, Gratama JW, Foekens JA, Sleijfer S. Towards a personalized breast cancer treatment approach guided by circulating tumor cell (CTC) characteristics. Cancer Treat. Rev. 2013;39(7):691-700. doi: 10.1016/j.ctrv.2013.04.001
  5. Tonak J, Gall FP, Hohenberge W, Hermanek P, Mühe E, Angermann B. Prinzipien der chirurgie maligner tumoren. In: Gall FP, Hermanek P, Tonak J, editors. Chirurgische Onkologie. Springer Link; 1986. p. 131-53. https://link.springer.com/chapter/10.1007/978-3-642-69600-8_8
  6. Miller MC, Doyle GV, Terstappen LW. Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer. J Oncol. 2010;2010:617421. doi: 10.1155/2010/617421
  7. Swaby RF, Cristofanilli M. Circulating tumor cells in breast cancer: a tool whose time has come of age. BMC Med. 2011;9:43. doi: 10.1186/1741-7015-9-43
  8. Antonio N, Bønnelykke-Behrndtz ML, Ward LC, Collin J, Christensen IJ, Steiniche T, Schmidt H, Feng Y, Martin1 P. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. EMBO J. 2015;2; 34(17):2219-2236. doi: 10.15252/embj.201490147
  9. Makki J. Diversity of breast carcinoma: histological subtypes and clinical relevance. Clin Med Insights Pathol. 2015;8:23-31. doi: 10.4137/CPath.S31563
  10. Toss A, Cristofanilli M. Molecular characterization and targeted therapeutic approaches in breast cancer. Breast Cancer Res. 2015;17(1):60 doi: 10.1186/s13058-015-0560-9
  11. Sleeman JP, Christofori G, Fodde R, Collard JG, Berx G, Decraene C, Ruegg C. Concepts of metastasis in flux: the stromal progression model. Semin Cancer Biol. 2012; 22(3):174-86. doi: 10.1016/j.semcancer.2012.02.007.
  12. Wu S, Liu S, Liu Z, Huang J, Pu X, Li J, Yang D, Deng H, Yang N, Xu J. Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One. 2015;24;10(4):e0123976. doi: 10.1371/journal.pone.0123976.
  13. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland- Jones B, Srkalovic G, Tejwani S, Schott AF, ORourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol. 2014;32(31):3483-89. doi: 10.1200/JCO.2014.56.2561
  14. Patel P, Chen EI. Cancer stem cells, tumor dormancy, and metastasis. Front Endocrinol (Lausanne). 2012;23;3:125. doi: 10.3389/fendo.2012.00125
  15. Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MM. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients. BMJ (Clinical research ed). 2015;351:h4901. doi: 10.1136/bmj.h4901
Address for correspondence:
210023, The Republic of Belarus,
Vitebsk, Frunze Ave., 27,
Vitebsk State Medical University,
Department of Oncology
With the Courses
Of RD, RT, FST and SRT,
Tel. office: +375 212 57-64-16,
e-mail: Evgenij-shlyakhtunov@yandex.ru,
Yauheni A. Shliakhtunou
Information about the authors:
Shliakhtunou Yauheni A., PhD, Associate Professor of the Department of Oncology with the Courses of RD, RT, FST and SRT, Vitebsk State Medical University, Vitebsk, Republic of Belarus.
https://orcid.org/0000-0002-5906-5373
Contacts | ©Vitebsk State Medical University, 2007