Cirkulujúce nádorové bunky u rakoviny prsníka – prehľad

Diseminované malignity sú zodpovedné za väčšinu úmrtí na rakovinu. Cirkulujúce nádorové bunky (circulating tumor cells – CTC) sú generované počas metastatického procesu. Prítomnosť CTC, epiteliálnych buniek nachádzajúcich sa v periférnej krvi, je povinný krok rozvoja vzdialených metastáz. Cirkulujúce epitelové bunky majú morfológiu malígnych buniek a ich počet v krvi koreluje s rozsahom nádorovej choroby. Na detekciu CTC v periférnej krvi sú využívané dva hlavné prístupy:1) metóda využívajúca reakciu s protilátkou a 2) na detekcii nukleových kyselín založené techniky. Nádorové bunky s HER‑ 2 overexpresiou sú často rezistentné na cytotoxickú liečbu a rádioterapiu. Širšie klinické použitie detekcie minimálnej zvyškovej choroby je čiastočne obmedzené nedostatkom štandardizovaných metód detekcie. Nedávne štúdie naznačujú, že okrem prognostického významu nádorových buniek môže byť ich stanovenie dôležité pri liečbe a následnom sledovaní pacienta, alebo ako potenciálne ciele pre cielenú terapiu. Perzistencia minimálnej reziduálnej/ zvyškovej choroby po primárnej liečbe môže byť indíciou na podanie rozsiahlej adjuvantnej liečby, aby sa zabránilo relapsu ochorenia. Detekcia CTC a využívanie prognostických markerov, ako je HER‑ 2 overexpresia, môže napomôcť lepšie pochopiť biológiu a klinický význam prítomnosti CTC u pacientov s karcinómom prsníka.

Kľúčové slová:
metastatická rakovina prsníka – cirkulujúce nádorové bunky – minimálna reziduálna/ zvyšková choroba

Autoři: B. Vertakova Krakovska ^1,2; L. Sanislo ³; S. Spanik ^1,2; J. Svec ^1,4; D. Ondrus ¹
Působiště autorů: Department of Medical Oncology, St. Elizabeth Cancer Institute, Bratislava, Slovak Republic ²; Department of Clinical Immunology and Allergology, St. Elizabeth Cancer Institute, Bratislava, Slovak Republic ³; Department of Oncology, Slovak Medical University, Bratislava, Slovak Republic ⁴; st Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic ¹¹
Vyšlo v časopise: Klin Onkol 2010; 23(2): 86-91
Kategorie: Přehledy

Souhrn

Kľúčové slová:
metastatická rakovina prsníka – cirkulujúce nádorové bunky – minimálna reziduálna/ zvyšková choroba

Zdroje

1. De Vita VT Jr. Breast cancer therapy: exercising all our options. N Engl J Med 1989; 320(8): 527– 529.

2. Jacob C, Sollier C, Jabado N. Circulating tumor cells: detection, molecular profiling and future prospects. Expert Rev Proteomics 2007; 4(6): 741– 756.

3. Rosner D, Lane WW. Predicting recurrence in axillary‑ node negative breast cancer patients. Breast Cancer Res Treat 1993; 25(2): 127– 139.

4. Diel IJ, Neumaier M, Schuetz F. Bone marrow micrometastases and circulating tumor cells. In: Harris JR, Lippman ME, Morrow M et al (eds). Diseases of the Breast. 3rd ed. Philadelphia: Lippincott Williams and Wilkins 2005: 697– 707.

5. Janni W, Rack B, Lindemann K et al. Detection of micrometastatic disease in bone marrow: Is it ready for prime time? [http:/ / www.theoncologist.aplhamedpress.org/ cgi/ content/ full/ 10/ 7/ 480/ T1].

6. Klein CHA, Blakennstein T, Schmidt‑ Kittler O et al. Genetic heterogenity of single disseminated tumor cells in minimal residual cancer. Lancet 2002; 360(9334): 683– 689.

7. Lang J, Hall E, Carolyn S. Significance of micrometastasis in bone marrow and blood of perable breast cancer patients: research tool or clinical application. Expert Rev Anticancer Ther 2007; 7(10): 1463– 1472.

8. Balic M, Dandachi N, Hofmann G et al. Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Cytometry B Clin Cytom 2005; 68(1): 25– 30.

9. Diel IJ, Kaufmann M, Costa SD et al. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 1996; 88(22): 1652– 1658.

10. Wiedswang G, Borgen E, Karesen R et al. Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 2003; 21(18): 3469– 3478.

11. Pantel K, Izbicki J, Passlick B et al. Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non‑small‑cell lung cancer without overt metastases. Lancet 1996; 347(9002): 649– 653.

12. Lindemann F, Schlimok G, Dirschedl P et al. Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet 1992; 340(8821): 685– 689.

13. Lacroix M. Significance, detection and markers of disseminated breast cancer cells‑ review. Endocr Relat Cancer 2006; 13(4): 1033– 1067.

14. Vincent‑ Salomon A, Bicard FC, Pierga JY. Bone marrow micrometastasis in breast cancer: review of detection methods, preognostic impact and biological issues. J Clin Pathol 2008; 61(5): 570– 576.

15. Witzig TE, Bossy B, Kimlinger T et al. Detection of circulating cytokeratin positive cells in the blood of breast cancer patients using immunomagnetic enrichment and digital microscopy. Clin Cancer Res 2002; 8(5): 1085– 1091.

16. Gilbey AM, Burnett D, Coleman RE et al. The detection of circulating breast cancer cells in blood. J Clin Path 2004; 57(9): 903– 911.

17. Tveito S, Naelandsmo G, Hoifodt H. Specific isolation of disseminated cancer cells: a new method permitting sensitive detection of target moleculaes of diagnostic and therapeutig value. Clin Exp Metast 2007; 24(5): 317– 327.

18. Galbavy S, Kuliffay P. Laser scanning cytometry (LSC) in pathology – a perspective tool for the future? Bratisl Med J 2008; 109(1): 3– 7.

19. Zabaglo L, Ormerod MG, Parton M et al. Cell filtration‑ laser scanning cytometry for the characterisation of circulating breast cancer cells. Cytometry A 2003; 55(2): 102– 108.

20. He W, Wang H, Hartmann LC et al. In vivo quantification of rare circulating tumor cells by multiphoton intravital flow cytometry. Proc Nat Acad Sci 2007; 104(28): 11760– 11765.

21. Anker P, Mulcahy H, Chen WQ et al. Detection of circulanting tumor DNA in the blood/ plasma/ serum of cancer patients. Cancer Metast Rev 1999; 18(1): 65– 73.

22. Fehm T, Becker S, Becker‑ Pergola G et al. Presence of apoptoic and nonapoptoic disseminated tumor cells reflects the response to neoadjuvant systemic therapy in breast cancer [monograph on the Internet]. Breast Cancer Res 2006; 8(5): R60.

23. Bivén K, Erdal H, Hägg M et al. A novel assay for discovery and characterization of pro‑apoptoic drugs and for monitoring apoptosis in patient sera. Apoptosis 2003; 8(3): 263– 268.

24. Sarrio D, Rodriguez‑ Pinilla SM, Hardisson D et al. Epithelial‑ mesenchymal transition in breast cancer relates to the basal‑like phenotype. Cancer Res 2008; 68(4): 989– 997.

25. Thiery JP. Epithelial‑ mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2(6): 442– 454.

26. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008; 8(10): 755– 768.

27. Mani SA, Yang J, Brooks M et al. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal‑like breast cancers. Proc Natl Acad Sci USA 2007; 104(24): 10069– 10074.

28. Balic M, Lin H, Young L et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 2006; 12(19): 5615– 5621.

29. Theodoropoulos PA, Polioudaki H, Sanidas E et al. Detection of circulating tumor cells with breast cancer stem cell‑like phenotype in blood samples of patients with breast cancer. Proc Am Assoc Cancer Res 2008; 49: 452.

30. Aktas B, Tewes M, Fehm T et al. Stem cell and epithelial‑ mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 2009, 11(4): R46.

31. Open Access cancer journal from The European Institute of Oncology. SABCS congress news: CTCs that undergo EMT may escape conventional detection [http:/ / www.ecancermedicalscience.com/ news‑ insider‑ news.asp?itemId=848].

32. Camara O, Kavallaris A, Nöschel H et al. Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells. World J Surg Oncol 2006; 4: 67.

33. Pachmann K, Camara O, Kavallaris A et al. Quantification of the response of circulating epithelial cells to neoadjuvant treatment for breast cancer: a new tool for therapy monitoring. Breast Cancer Res 2005; 7(6): R975– R979.

34. Esteva FJ. Commentary: can circulating HER‑ 2 extracellular domain predict response to trastuzumab in HER‑ 2 negative breast cancer? Oncologist 2008; 13(4): 370– 372.

35. Meng S, Tripathy D, Shete S et al. HER‑ 2 gene amplification can be acquired as breast cancer progresses. PNAS 2004; 101(25): 9393– 9398.

36. Wulfing P, Borchard J, Buerger H et al. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res 2006; 12(6): 1715– 1720.

37. Cristofanili M. Circulating tumor cells and endothelial cells as predictors of response in metastatic breast cancer. Breast Cancer Research 2007; 9.