본문 바로가기
KERD
논문KCI 등재

유방암에서의 순환종양세포: 검출시스템, 분자적 특성해석, 그리고 앞으로의 과제

Circulating Tumor Cells in Breast Cancer: Detection Systems, Molecular Characterization, and Future Challenges

2

조회

0

다운로드

0

인용

0

참고문헌

초록

Background: Circulating tumor cell (CTC) analysis is a promising new diagnostic field for estimating the risk for metastatic relapse and metastatic progression in patients with cancer. Content: Different analytical systems for CTC isolation and detection have been developed as immunocytochemical and molecular assays, most including separation steps by size or biological characteristics, such as expression of epithelial- or cancer-specific markers. Recent technical advancements in CTC detection and characterization include methods based on multiplex reverse-transcription quantitative PCR and approaches based on imaging and microfilter and microchip devices. New areas of research are directed toward developing novel assays for CTC molecular characterization. QC is an important issue for CTC analysis, and standardization of micrometastatic cell detection and characterization methodologies is important for the incorporation of CTCs into prospective clinical trials to test their clinical utility. The molecular characterization of CTCs can provide important information on the molecular and biological nature of these cells, such as the status of hormone receptors and epidermal and other growth factor receptor family members, and indications of stem-cell characteristics. This information is important for the identification of therapeutic targets and resistance mechanisms in CTCs as well as for the stratification of patients and real-time monitoring of systemic therapies. Summary: CTC analysis can be used as a liquid biopsy approach for prognostic and predictive purposes in breast and other cancers. In this review we focus on state-of-the-art technology platforms for CTC isolation, imaging, and detection; QC of CTC analysis; and ongoing challenges for the molecular characterization of CTCs.

Abstract

Background: Circulating tumor cell (CTC) analysis is a promising new diagnostic field for estimating the risk for metastatic relapse and metastatic progression in patients with cancer. Content: Different analytical systems for CTC isolation and detection have been developed as immunocytochemical and molecular assays, most including separation steps by size or biological characteristics, such as expression of epithelial- or cancer-specific markers. Recent technical advancements in CTC detection and characterization include methods based on multiplex reverse-transcription quantitative PCR and approaches based on imaging and microfilter and microchip devices. New areas of research are directed toward developing novel assays for CTC molecular characterization. QC is an important issue for CTC analysis, and standardization of micrometastatic cell detection and characterization methodologies is important for the incorporation of CTCs into prospective clinical trials to test their clinical utility. The molecular characterization of CTCs can provide important information on the molecular and biological nature of these cells, such as the status of hormone receptors and epidermal and other growth factor receptor family members, and indications of stem-cell characteristics. This information is important for the identification of therapeutic targets and resistance mechanisms in CTCs as well as for the stratification of patients and real-time monitoring of systemic therapies. Summary: CTC analysis can be used as a liquid biopsy approach for prognostic and predictive purposes in breast and other cancers. In this review we focus on state-of-the-art technology platforms for CTC isolation, imaging, and detection; QC of CTC analysis; and ongoing challenges for the molecular characterization of CTCs.

참고문헌 (75)

  1. Ashworth TR, "A case of cancer in which cells similar to those in the tumours were seen in the blood after death", Med J Australia, 14, pp.146~147 (1869)
  2. Fidler IJ, "The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited", Nat Rev Cancer, 3, pp.453~458 (2003)
  3. Kaiser J., "Cancer’s circulation problem", Science, 327, pp.1072~1074 (2010)
  4. Pantel K, "Cancer micrometastases", Nat Rev Clin Oncol, 6, pp.339~351 (2009)
  5. Hayes DF, "Is there a role for circulating tumor cells in the management of breast cancer?", Clin Cancer Res, 14, pp.3646~3650 (2008)
  6. Kasimir-Bauer S, "Circulating tumor cells as markers for cancer risk assessment and treatment monitoring", Mol Diagn Ther, 13, pp.209~215 (2009)
  7. Braun S, "A pooled analysis of bone marrow micrometastasis in breast cancer", N Engl J Med, 353, pp.793~802 (2005)
  8. Stathopoulou A, "Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance", J Clin Oncol, 20, pp.3404~3412 (2002)
  9. Xenidis N, "Peripheral blood circulating cytokeratin-19 mRNApositive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer", Ann Oncol, 14, pp.849~855 (2003)
  10. Xenidis N, "Predictive and prognostic value of peripheral blood cytokeratin- 19 mRNA-positive cells detected by real-time polymerase chain reaction in nodenegative breast cancer patients", J Clin Oncol, 24, pp.3756~3762 (2006)
  11. Ignatiadis M, "Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer", Clin Cancer Res, 14, pp.2593~2600 (2008)
  12. Ignatiadis M, "Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer", J Clin Oncol, 25, pp.5194~5202 (2007)
  13. Xenidis N, "Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer", J Clin Oncol, 27, pp.2177~2184 (2009)
  14. Cristofanilli M, "Circulating tumor cells, disease progression, and survival in metastatic breast cancer", N Engl J Med, 351, pp.781~791 (2004)
  15. Mostert B, "Circulating tumor cells (CTCs): detection methodsand their clinical relevance in breast cancer", Cancer Treat Rev, 35, pp.463~474 (2009)
  16. Lianidou ES, "What’s new on circulating tumor cells? A meeting report", Breast Cancer Res, 12, pp.307~ (2010)
  17. Tibbe AG, "Statistical considerations for enumeration of circulating tumor cells", Cytometry A, 71, pp.154~162 (2007)
  18. Fehm T, "Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells", Cytotherapy, 7, pp.171~185 (2005)
  19. Königsberg R, "Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients", Acta Oncol, 50, pp.700~710 (2011)
  20. Sieuwerts AM, "Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells", J Natl Cancer Inst, 101, pp.61~66 (2009)
  21. Mostert B, "Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146", Breast Cancer Res Treat, 127, pp.33~41 (2011)
  22. Schindlbeck C, "Immunomagnetic enrichment of disseminated tumor cells in bone marrow and blood of breast cancer patients by the Thomsen-Friedenreich- Antigen", Clin Exp Metastasis, 25, pp.233~240 (2008)
  23. Deng G, "Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients", Breast Cancer Res, 10, pp.69~ (2008)
  24. Vona G, "Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells", Am J Pathol, 156, pp.57~63 (2000)
  25. Lin HK, "Portable filter-based microdevice for detection and characterization of circulating tumor cells", Clin Cancer Res, 16, pp.5011~5018 (2010)
  26. Zheng S, "3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood", Biomed Microdevices, 13, pp.203~213 (2011)
  27. Nagrath S, "Isolation of rare circulating tumour cells in cancer patients by microchip technology", Nature, 450, pp.1235~1239 (2007)
  28. Stott SL, "Isolation of circulating tumor cells using a microvortex-generating herringbone- chip", Proc Natl Acad Sci U S A, 107, pp.18392~18397 (2010)
  29. Adams AA, "Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor", J Am Chem Soc, 130, pp.8633~8641 (2008)
  30. Wang X, "Detection of circulating tumor cells in human peripheral blood using surfaceenhanced raman scattering nanoparticles", Cancer Res, 71, pp.1526~1532 (2011)
  31. Pachmann K, "Standardized quantification of circulating peripheral tumor cells from lung and breast cancer", Clin Chem Lab Med, 43, pp.617~627 (2005)
  32. Riethdorf S, "Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system", Clin Cancer Res, 13, pp.920~8 (2007)
  33. Balic M, "Novel immunofluorescence protocol for multimarker assessment of putative disseminating breast cancer stem cells", Appl Immunohistochem Mol Morphol, 19, pp.33~40 (2011)
  34. Bustin SA, "The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments", Clin Chem, 55, pp.611~622 (2009)
  35. Slade MJ, "Quantitative polymerase chain reaction for the detection of micrometastases in patients with breast cancer", J Clin Oncol, 17, pp.870~879 (1999)
  36. Stathopoulou A, "Real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler system", Clin Cancer Res, 9, pp.5145~5151 (2003)
  37. Stathopoulou A, "A highly specific real-time RT-PCR method for the quantitative determination of CK-19 mRNA positive cells in peripheral blood of patients with operable breast cancer", Int J Cancer, 119, pp.1654~1659 (2006)
  38. Ring AE, "Detection of circulating epithelial cells in the blood of patients with breast cancer. Comparison of three techniques", Br J Cancer, 92, pp.906~912 (2005)
  39. Fehm T, "A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation", Cancer, 107, pp.885~892 (2006)
  40. Obermayr E, "Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients", BMC Cancer, 10, pp.666~ (2010)
  41. Reinholz MM, "Evaluation of a panel of tumor markers for molecular detection of circulating cancer cells in women with suspected breast cancer", Clin Cancer Res, 11, pp.3722~3732 (2005)
  42. Aktas B, "Stem cell and epithelialmesenchymal transition markers are frequentlyoverexpressed in circulating tumor cells of metastatic breast cancer patients", Breast Cancer Res, 11, pp.46~ (2009)
  43. Fehm T, "Wallwiener D, et al. Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RTPCR and comparison to status of bone marrow disseminated cells", Breast Cancer Res, 11, pp.59~ (2009)
  44. Sieuwerts AM, "Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR", Breast Cancer Res Treat, 118, pp.455~468 (2009)
  45. Markou A, "Molecular characterization of circulating tumor cells in breast cancer by a liquidbead array hybridization assay", Clin Chem, 57, pp.421~430 (2011)
  46. Alix-Panabières C, "Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer", Breast Cancer Res, 11, pp.39~ (2009)
  47. Khleif SN, "AACR-FDA-NCI Cancer Biomarkers Collaborative. AACR-FDA-NCI Cancer Biomarkers Collaborative consensus report: advancing the use of biomarkers in cancer drug development", Clin Cancer Res, 16, pp.3299~3318 (2010)
  48. Fehm T, "HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial", Breast Cancer Res Treat, 124, pp.403~412 (2010)
  49. Kraan J, "External quality assurance of circulating tumor cell enumeration using the CellSearch® system: a feasibility study", Cytometry B Clin Cytom, 80, pp.112~118 (2011)
  50. Balic M, "Comparison of two methods for enumerating circulating tumor cells in carcinoma patients", Cytometry B Clin Cytom, 68, pp.25~30 (2005)
  51. Punnoose EA, "Molecular biomarker analyses using circulating tumor cells", PLoS One, 5, pp.12517~ (2010)
  52. Becker S, "Evaluation of a RT-PCR based routine screening tool for the detection of disseminated epithelial cells in the bone marrow of breast cancer patients", Breast Cancer Res Treat, 117, pp.227~233 (2009)
  53. Van der Auwera I, "Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19", mammaglobin RT-PCR in patients with metastatic breast cancer, 2010, pp.102, 276~284
  54. Mego M, "Cristofanilli M. Molecular mechanisms of metastasis in breast cancerclinical applications", Nat Rev Clin Oncol, 7, pp.693~701 (2010)
  55. Kallergi G, "Hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients", Breast Cancer Res, 11, pp.84~ (2009)
  56. Tewes M, "Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies", Breast Cancer Res Treat, 115, pp.581~590 (2009)
  57. Meng S, "HER-2 gene amplification can be acquired as breast cancer progresses", Proc Natl Acad Sci U S A, 101, pp.9393~9398 (2004)
  58. Bozionellou V, "Trastuzumab administration can effectively target chemotherapy-resistant cytokeratin-19 messenger RNA-positive tumor cells in the peripheral blood and bone marrow of patients with breast cancer", Clin Cancer Res, 10, pp.8185~8194 (2004)
  59. Riethdorf S, "Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial", Clin Cancer Res, 16, pp.2634~2645 (2010)
  60. Cao S, "Quantitative determination of HER2 expression by confocal microscopy assay in CTCs of breast cancer", Oncol Rep, 23, pp.423~428 (2010)
  61. Ignatiadis M, "HER2-positive circulating tumor cells in breast cancer", PLoS One, 6, pp.15624~ (2011)
  62. Apostolaki S, "Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance", Ann Oncol, 18, pp.851~858 (2007)
  63. Flores LM, "Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer", Br J Cancer, 102, pp.1495~1502 (2010)
  64. Munzone E, "Changes of HER2 status in circulating tumor cells compared with the primary tumor during treatment for advanced breast cancer", Clin Breast Cancer, 10, pp.392~397 (2010)
  65. Payne RE, "Measurements of EGFR expression on circulating tumor cells are reproducible over time in metastatic breast cancer patients", harmacogenomics, 10, pp.51~57 (2009)
  66. Liu Z, "Eradication of EGFR-positive circulating tumor cells and objective tumor response with lapatinib and capecitabine", Cancer Biol Ther, 10, pp.860~864 (2010)
  67. Ntoulia M, "Detection of Mammaglobin A-mRNA-positive circulating tumor cells in peripheral blood of patients with operable breast cancer with nested RT-PCR", Clin Biochem, 39, pp.879~887 (2006)
  68. Diehn M, "Therapeutic implications of the cancer stem cell hypothesis", Semin Radiat Oncol, 19, pp.78~86 (2009)
  69. Meng S, "Circulating tumor cells in patients with breast cancer dormancy", Clin Cancer Res, 10, pp.8152~8162 (2004)
  70. Korkaya H, "HER2 regulates the mammary stem", progenitor cell population driving tumorigenesis and invasion, 2008, pp.27, 6120~6130
  71. Bonnomet A, "Epithelial-tomesenchymal transitions and circulating tumor cells", J Mammary Gland Biol Neoplasia, 15, pp.261~273 (2010)
  72. Balic M, "Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype", Clin Cancer Res, 12, pp.5615~5621 (2006)
  73. Theodoropoulos PA, "Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer", Cancer Lett, 288, pp.99~106 (2010)
  74. Magnifico A, "Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab", Clin Cancer Res, 15, pp.2010~2021 (2009)
  75. Klein CA, "Parallel progression of primary tumours and metastases", Nat Rev Cancer, 9, pp.302~312 (2009)

관련 논문AI추천

이 간행물의 다른 논문 (7건)