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Journal of Oncology
Volume 2010, Article ID 392652, 9 pages
http://dx.doi.org/10.1155/2010/392652
Review Article

Circulating Tumor Cells in Gastrointestinal Malignancies: Current Techniques and Clinical Implications

1Department of Visceral- and Transplantation Surgery, Department of Surgery, University Hospital Zurich, 8091 Zurich, Switzerland
2Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, 45122 Essen, Germany

Received 12 April 2009; Accepted 28 September 2009

Academic Editor: Vassilis Georgoulias

Copyright © 2010 Georg Lurje et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. H. C. Engell, “Cancer cells in the circulating blood; a clinical study on the occurrence of cancer cells in the peripheral blood and in venous blood draining the tumour area at operation,” Ugeskr Laeger, vol. 117, pp. 822–823, 1955. View at Google Scholar
  2. A. Ulmer, O. Schmidt-Kittler, J. Fischer et al., “Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells,” Clinical Cancer Research, vol. 10, no. 2, pp. 531–537, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Fehm, A. Sagalowsky, E. Clifford et al., “Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant,” Clinical Cancer Research, vol. 8, no. 7, pp. 2073–2084, 2002. View at Google Scholar · View at Scopus
  4. J. Folkman, “Tumor angiogenesis: therapeutic implications,” The New England Journal of Medicine, vol. 285, no. 21, pp. 1182–1186, 1971. View at Google Scholar · View at Scopus
  5. J. Folkman, “Angiogenesis in cancer, vascular, rheumatoid and other disease,” Nature Medicine, vol. 1, no. 1, pp. 27–31, 1995. View at Google Scholar · View at Scopus
  6. G. Lurje, W. Zhang, and H.-J. Lenz, “Molecular prognostic markers in locally advanced colon cancer,” Clinical Colorectal Cancer, vol. 6, no. 10, pp. 683–690, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Lurje, W. Zhang, A. M. Schultheis et al., “Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer,” Annals of Oncology, vol. 19, no. 10, pp. 1734–1741, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. R. M. Strieter, “Masters of angiogenesis,” Nature Medicine, vol. 11, no. 9, pp. 925–927, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. Y. I. Elshimali and W. W. Grody, “The clinical significance of circulating tumor cells in the peripheral blood,” Diagnostic Molecular Pathology, vol. 15, no. 4, pp. 187–194, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Paget, “The distribution of secondary growths in cancer of the breast,” The Lancet, vol. 133, no. 3421, pp. 571–573, 1889. View at Google Scholar · View at Scopus
  11. I. J. Fidler, “The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited,” Nature Reviews Cancer, vol. 3, no. 6, pp. 453–458, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. I. J. Fidler and G. Poste, “The “seed and soil” hypothesis revisited,” The Lancet Oncology, vol. 9, no. 8, p. 808, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Mukai, “Occult neoplastic cells and malignant micro-aggregates in lymph node sinuses: review and hypothesis,” Oncology Reports, vol. 14, no. 1, pp. 173–175, 2005. View at Google Scholar · View at Scopus
  14. M. Al-Hajj and M. F. Clarke, “Self-renewal and solid tumor stem cells,” Oncogene, vol. 23, pp. 7274–7282, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Brittan and N. A. Wright, “Stem cell in gastrointestinal structure and neoplastic development,” Gut, vol. 53, no. 6, pp. 899–910, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Gudjonsson and M. K. Magnusson, “Stem cell biology and the cellular pathways of carcinogenesis,” APMIS, vol. 113, no. 11-12, pp. 922–929, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Pohl, G. Lurje, M. Kahn, and H.-J. Lenz, “Stem cells in colon cancer,” Clinical Colorectal Cancer, vol. 7, no. 2, pp. 92–98, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Baba, S. Natsugoe, M. Shimada et al., “Prospective evaluation of preoperative chemotherapy in resectable squamous cell carcinoma of the thoracic esophagus,” Diseases of the Esophagus, vol. 13, no. 2, pp. 136–141, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. C. S. Potten and M. Loeffler, “Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt,” Development, vol. 110, no. 4, pp. 1001–1020, 1990. View at Google Scholar · View at Scopus
  20. W. M. Wong and N. A. Wright, “Cell proliferation in gastrointestinal mucosa,” Journal of Clinical Pathology, vol. 52, no. 5, pp. 321–333, 1999. View at Google Scholar · View at Scopus
  21. G. Lurje, A. E. Hendifar, A. M. Schultheis et al., “Polymorphisms in interleukin 1 beta and interleukin 1 receptor antagonist associated with tumor recurrence in stage II colon cancer,” Pharmacogenetics and Genomics, vol. 19, no. 2, pp. 95–102, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. B. Hotz, M. Arndt, S. Dullat, S. Bhargava, H.-J. Buhr, and H. G. Hotz, “Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer,” Clinical Cancer Research, vol. 13, no. 16, pp. 4769–4776, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Pantel and R. H. Brakenhoff, “Dissecting the metastatic cascade,” Nature Reviews Cancer, vol. 4, no. 6, pp. 448–456, 2004. View at Google Scholar · View at Scopus
  24. H. Schwarzenbach, C. Alix-Panabières, I. Müller et al., “Cell-free tumor DNA in blood plasma as a marker for circulating tumor cells in prostate cancer,” Clinical Cancer Research, vol. 15, no. 3, pp. 1032–1038, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Jacob, C. Sollier, and N. Jabado, “Circulating tumor cells: detection, molecular profiling and future prospects,” Expert Review of Proteomics, vol. 4, no. 6, pp. 741–756, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Kang and J. Massagué, “Epithelial-mesenchymal transitions: twist in development and metastasis,” Cell, vol. 118, no. 3, pp. 277–279, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Wittekind and M. Neid, “Cancer invasion and metastasis,” Oncology, vol. 69, supplement 1, pp. 14–16, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. A. B. Al-Mehdi, K. Tozawa, A. B. Fisher, L. Shientag, A. Lee, and R. J. Muschel, “Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis,” Nature Medicine, vol. 6, no. 1, pp. 100–102, 2000. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Paterlini-Brechot and N. L. Benali, “Circulating tumor cells (CTC) detection: clinical impact and future directions,” Cancer Letters, vol. 253, no. 2, pp. 180–204, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. A.-C. Hoffmann, J. Brabender, R. Metzger et al., “Dihydropyrimidine dehydrogenase mRNA expression in peripheral blood of rectal cancer patients is significantly associated with residual tumor and distant metastases following resection,” Journal of Surgical Oncology, vol. 99, no. 5, pp. 296–301, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. A.-C. Hoffmann, U. Warnecke-Eberz, T. Luebke et al., “Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers,” Journal of Surgical Oncology, vol. 95, no. 1, pp. 51–54, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. J. B. Smerage and D. F. Hayes, “The measurement and therapeutic implications of circulating tumour cells in breast cancer,” British Journal of Cancer, vol. 94, no. 1, pp. 8–12, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. S. J. Cohen, C. J. A. Punt, N. Iannotti et al., “Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer,” Journal of Clinical Oncology, vol. 26, no. 19, pp. 3213–3221, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Gertler, R. Rosenberg, K. Fuehrer, M. Dahm, H. Nekarda, and J. R. Siewert, “Detection of circulating tumor cells in blood using an optimized density gradient centrifugation,” Recent Results in Cancer Research, vol. 162, pp. 149–155, 2003. View at Google Scholar · View at Scopus
  35. C. Griwatz, B. Brandt, G. Assmann, and K. S. Zänker, “An immunological enrichment method for epithelial cells from peripheral blood,” Journal of Immunological Methods, vol. 183, no. 2, pp. 251–265, 1995. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Cristofanilli, G. T. Budd, M. J. Ellis et al., “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” The New England Journal of Medicine, vol. 351, no. 8, pp. 781–791, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. G. Vona, A. Sabile, M. Louha et al., “Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells,” American Journal of Pathology, vol. 156, no. 1, pp. 57–63, 2000. View at Google Scholar · View at Scopus
  38. C. S. Mitsiades, P. Lembessis, A. Sourla, C. Milathianakis, A. Tsintavis, and M. Koutsilieris, “Molecular staging by RT-PCR analysis for PSA and PSMA in peripheral blood and bone marrow samples is an independent predictor of time to biochemical failure following radical prostatectomy for clinically localized prostate cancer,” Clinical and Experimental Metastasis, vol. 21, no. 6, pp. 495–505, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. W. De Roock, H. Piessevaux, J. De Schutter et al., “KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab,” Annals of Oncology, vol. 19, no. 3, pp. 508–515, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. F. Di Fiore, F. Blanchard, F. Charbonnier et al., “Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy,” British Journal of Cancer, vol. 96, no. 8, pp. 1166–1169, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Lièvre, J.-B. Bachet, V. Boige et al., “KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab,” Journal of Clinical Oncology, vol. 26, no. 3, pp. 374–379, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Holdhoff, K. Schmidt, R. Donehower, and L. A. Diaz Jr., “Analysis of circulating tumor DNA to confirm somatic KRAS mutations,” Journal of the National Cancer Institute, vol. 101, no. 18, pp. 1284–1285, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. Z. Liu, M. Jiang, J. Zhao, and H. Ju, “Circulating tumor cells in perioperative esophageal cancer patients: quantitative assay system and potential clinical utility,” Clinical Cancer Research, vol. 13, no. 10, pp. 2992–2997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. A.-C. Hoffmann, D. Vallbohmer, K. Prenzel et al., “Methylated DAPK and APC promoter DNA detection in peripheral blood is significantly associated with apparent residual tumor and outcome,” Journal of Cancer Research and Clinical Oncology, vol. 135, no. 9, pp. 1231–1237, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. J.-C. Goeminne, T. Guillaume, and M. Symann, “Pitfalls in the detection of disseminated non-hematological tumor cells,” Annals of Oncology, vol. 11, no. 7, pp. 785–792, 2000. View at Publisher · View at Google Scholar · View at Scopus
  46. W. J. Allard, J. Matera, M. C. Miller et al., “Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases,” Clinical Cancer Research, vol. 10, no. 20, pp. 6897–6904, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Alix-Panabières, S. Riethdorf, and K. Pantel, “Circulating tumor cells and bone marrow micrometastasis,” Clinical Cancer Research, vol. 14, no. 16, pp. 5013–5021, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. R. A. Ghossein and S. Bhattacharya, “Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours,” European Journal of Cancer, vol. 36, no. 13, pp. 1681–1694, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. H. Nakanishi, Y. Kodera, and M. Tatematsu, “Molecular method to quantitatively detect micrometastases and its clinical significance in gastrointestinal malignancies,” Advances in Clinical Chemistry, vol. 38, pp. 87–110, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Mori, K. Mimori, H. Ueo et al., “Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease,” International Journal of Cancer, vol. 68, no. 6, pp. 739–743, 1996. View at Publisher · View at Google Scholar · View at Scopus
  51. V. Zieglschmid, C. Hollmann, and O. Böcher, “Detection of disseminated tumor cells in peripheral blood,” Critical Reviews in Clinical Laboratory Sciences, vol. 42, no. 2, pp. 155–196, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. P. Ruud, O. Fodstad, and E. Hovig, “Identification of a novel cytokeratin 19 pseudogene that may interfere with reverse transcriptase-polymerase chain reaction assays used to detect micrometastatic tumor cells,” International Journal of Cancer, vol. 80, no. 1, pp. 119–125, 1999. View at Publisher · View at Google Scholar · View at Scopus
  53. G. Mitropapas, A. Nezos, A. Halapas et al., “Molecular detection of tyrosinase transcripts in peripheral blood from patients with malignant melanoma: correlation of PCR sensitivity threshold with clinical and pathologic disease characteristics,” Clinical Chemistry and Laboratory Medicine, vol. 44, no. 12, pp. 1403–1409, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Aerts, W. Wynendaele, R. Paridaens et al., “A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood,” Annals of Oncology, vol. 12, no. 1, pp. 39–46, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Stathopoulou, M. Ntoulia, M. Perraki et al., “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,” International Journal of Cancer, vol. 119, no. 7, pp. 1654–1659, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Nagrath, L. V. Sequist, S. Maheswaran et al., “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature, vol. 450, no. 7173, pp. 1235–1239, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. G. Lurje, F. Nagashima, W. Zhang et al., “Polymorphisms in cyclooxygenase-2 and epidermal growth factor receptor are associated with progression-free survival independent of K-ras in metastatic colorectal cancer patients treated with single-agent cetuximab,” Clinical Cancer Research, vol. 14, no. 23, pp. 7884–7895, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. L.-C. Yen, Y.-S. Yeh, C.-W. Chen et al., “Detection of KRAS oncogene in peripheral blood as a predictor of the response to cetuximab plus chemotherapy in patients with metastatic colorectal cancer,” Clinical Cancer Research, vol. 15, no. 13, pp. 4508–4513, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. H. Ito, T. Kanda, T. Nishimaki, H. Sato, S. Nakagawa, and K. Hatakeyama, “Detection and quantification of circulating tumor cells in patients with esophageal cancer by real-time polymerase chain reaction,” Journal of Experimental and Clinical Cancer Research, vol. 23, no. 3, pp. 455–464, 2004. View at Google Scholar · View at Scopus
  60. A. C. Hoffmann, D. Vallbohmer, J. Brabender et al., “Survivin mRNA levels in peripheral blood from patients with esophageal cancer decrease significantly following surgical resection and are influenced by neoadjuvant chemoradiation,” in Digestive Disease Week, Washington, DC, USA, 2007. View at Google Scholar
  61. D. M. Parkin, F. Bray, J. Ferlay, and P. Pisani, “Global cancer statistics,” CA: A Cancer Journal for Clinicians, vol. 55, no. 2, pp. 74–108, 2005. View at Google Scholar · View at Scopus
  62. D. Cunningham, W. H. Allum, S. P. Stenning et al., “Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer,” The New England Journal of Medicine, vol. 355, no. 1, pp. 11–20, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. F. Miyazono, S. Natsugoe, S. Takao et al., “Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery,” Annals of Surgery, vol. 233, no. 2, pp. 189–194, 2001. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Ikeguchi and N. Kaibara, “Detection of circulating cancer cells after a gastrectomy for gastric cancer,” Surgery Today, vol. 35, no. 6, pp. 436–441, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Hiraiwa, H. Takeuchi, H. Hasegawa et al., “Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers,” Annals of Surgical Oncology, vol. 15, no. 11, pp. 3092–3100, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. S. J. Cohen, R. K. Alpaugh, S. Gross et al., “Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer,” Clinical Colorectal Cancer, vol. 6, no. 2, pp. 125–132, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. S. J. Cohen, C. J. A. Punt, N. Iannotti et al., “Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer,” Annals of Oncology, vol. 20, no. 7, pp. 1223–1229, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. G. Y. Locker, S. Hamilton, J. Harris et al., “ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer,” Journal of Clinical Oncology, vol. 24, no. 33, pp. 5313–5327, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. G. Lurje, P. C. Manegold, Y. Ning, A. Pohl, W. Zhang, and H.-J. Lenz, “Thymidylate synthase gene variations: predictive and prognostic markers,” Molecular Cancer Therapeutics, vol. 8, no. 5, pp. 1000–1007, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. G. Lurje, W. Zhang, D. Yang et al., “Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer,” Pharmacogenetics and Genomics, vol. 18, no. 2, pp. 161–168, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Brabender, D. Vallböhmer, P. Grimminger et al., “ERCC1 RNA expression in peripheral blood predicts minor histopathological response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus,” Journal of Gastrointestinal Surgery, vol. 12, no. 11, pp. 1815–1821, 2008. View at Publisher · View at Google Scholar · View at Scopus