Skip to main content

Advertisement

SpringerLink
Log in

Biology and significance of circulating and disseminated tumour cells in colorectal cancer

  • Review Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

More than 130 years ago, circulating tumour cells (CTCs) and disseminated tumour cells (DTCs) have been linked to metastasis. Since then, a myriad of studies attempted to characterise and elucidate the clinical impact of CTCs/DTCs, amongst others in colorectal cancer (CRC). Due to a flood of heterogeneous findings regarding CTCs/DTCs in CRC, this review aims to describe the known facts about CTC/DTC biology and clinical impact.

Methods

To identify the basic scientific literature regarding the biology and clinical impact of CTCs/DTCs in CRC, we reviewed the literature in the PubMed database. We focused on publications written in English and published until January 2012. As search terms, we used “colorectal cancer (CRC)”, “colon cancer (CC)”, “CTC”, “DTC”, “bone marrow (BM)”, “lymph node (LN)”, “peripheral blood (PB)”, “significance” and “prognosis”.

Results

CTC detection and quantification under standardised conditions is feasible. Several studies in large patient settings have revealed prognostic impact of CTCs in CRC. CRC-derived DTC detection and analysis in BM exhibits a more heterogeneous picture but also shows clinical value. Furthermore, the presence of DTCs in LN has a strong prognostic impact in CRC.

Conclusions

Clinical relevance and prognostic significance of CTCs/DTCs in CRC have been clearly demonstrated in many experimental studies. The major challenge in CTC/DTC research is now to harmonise the various identification and detection approaches and consequently to conduct large prospective multi-institutional trials to verify the use of CTCs/DTCs as a valid prognostic and predictive biomarker for clinical routine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4(6):448–456

    PubMed  CAS  Google Scholar 

  2. Wolfrum F et al (2005) Detection and clinical implications of minimal residual disease in gastro-intestinal cancer. Langenbecks Arch Surg 390(5):430–441

    PubMed  Google Scholar 

  3. Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46(4):765–781

    PubMed  CAS  Google Scholar 

  4. Thorsteinsson M, Jess P (2011) The clinical significance of circulating tumor cells in non-metastatic colorectal cancer—a review. Eur J Surg Oncol 37(6):459–465

    PubMed  CAS  Google Scholar 

  5. Weitz J et al (2005) Colorectal cancer. Lancet 365(9454):153–165

    PubMed  Google Scholar 

  6. Hess KR et al (2006) Metastatic patterns in adenocarcinoma. Cancer 106(7):1624–1633

    PubMed  Google Scholar 

  7. Ashworth, TR (1869) A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Australian Medical Journal 14:146–7

    Google Scholar 

  8. Zhan M, Zhao H, Han ZC (2004) Signalling mechanisms of anoikis. Histol Histopathol 19(3):973–983

    PubMed  CAS  Google Scholar 

  9. Sachdev D et al (2010) The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival. Oncogene 29(2):251–262

    PubMed  CAS  Google Scholar 

  10. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3(6):453–458

    PubMed  CAS  Google Scholar 

  11. Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331(6024):1559–1564

    PubMed  CAS  Google Scholar 

  12. Thiery JP et al (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139(5):871–890

    PubMed  CAS  Google Scholar 

  13. Sun YF et al (2011) Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance. J Cancer Res Clin Oncol 137(8):1151–1173

    PubMed  Google Scholar 

  14. Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14(6):818–829

    PubMed  CAS  Google Scholar 

  15. Morel AP et al (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3(8):e2888

    PubMed  Google Scholar 

  16. Sabbah M et al (2008) Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat 11(4–5):123–151

    PubMed  CAS  Google Scholar 

  17. Vincan E et al (2007) A human three-dimensional cell line model allows the study of dynamic and reversible epithelial-mesenchymal and mesenchymal-epithelial transition that underpins colorectal carcinogenesis. Cells Tissues Organs 185(1–3):20–28

    PubMed  Google Scholar 

  18. Loboda A et al (2011) EMT is the dominant program in human colon cancer. BMC Med Genomics 4:9

    PubMed  Google Scholar 

  19. Lecharpentier A et al (2011) Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br J Cancer 105(9):1338–1341

    PubMed  CAS  Google Scholar 

  20. Hiratsuka S et al (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8(12):1369–1375

    PubMed  CAS  Google Scholar 

  21. Kang SY et al (2009) Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1. Proc Natl Acad Sci U S A 106(29):12115–12120

    PubMed  CAS  Google Scholar 

  22. Kaplan RN et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827

    PubMed  CAS  Google Scholar 

  23. Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6(6):449–458

    PubMed  CAS  Google Scholar 

  24. Weiss L (1990) Metastatic inefficiency. Adv Cancer Res 54:159–211

    PubMed  CAS  Google Scholar 

  25. Gout S, Tremblay PL, Huot J (2008) Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis. Clin Exp Metastasis 25(4):335–344

    PubMed  CAS  Google Scholar 

  26. Camerer E et al (2004) Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 104(2):397–401

    PubMed  CAS  Google Scholar 

  27. Nieswandt B et al (1999) Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res 59(6):1295–1300

    PubMed  CAS  Google Scholar 

  28. Hou JM et al (2011) Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol 178(3):989–996

    PubMed  Google Scholar 

  29. Pawelek JM, Chakraborty AK (2008) The cancer cell–leukocyte fusion theory of metastasis. Adv Cancer Res 101:397–444

    PubMed  CAS  Google Scholar 

  30. Abdel-Ghany M et al (2001) The breast cancer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis. J Biol Chem 276(27):25438–25446

    PubMed  CAS  Google Scholar 

  31. Brown DM, Ruoslahti E (2004) Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell 5(4):365–374

    PubMed  CAS  Google Scholar 

  32. Wang H et al (2004) Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J Cell Biol 164(6):935–941

    PubMed  CAS  Google Scholar 

  33. Kim MY et al (2009) Tumor self-seeding by circulating cancer cells. Cell 139(7):1315–1326

    PubMed  Google Scholar 

  34. Chang YS et al (2000) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A 97(26):14608–14613

    PubMed  CAS  Google Scholar 

  35. Brooks DE (1984) The biorheology of tumor cells. Biorheology 21(1–2):85–91

    PubMed  CAS  Google Scholar 

  36. Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8(5):329–340

    PubMed  CAS  Google Scholar 

  37. Smirnov DA et al (2005) Global gene expression profiling of circulating tumor cells. Cancer Res 65(12):4993–4997

    PubMed  CAS  Google Scholar 

  38. Solmi R et al (2006) Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer. BMC Cancer 6:250

    PubMed  Google Scholar 

  39. Zieglschmid V et al (2007) Tumor-associated gene expression in disseminated tumor cells correlates with disease progression and tumor stage in colorectal cancer. Anticancer Res 27(4A):1823–1832

    PubMed  Google Scholar 

  40. Lankiewicz S et al (2008) Tumour-associated transcripts and EGFR deletion variants in colorectal cancer in primary tumour, metastases and circulating tumour cells. Cell Oncol 30(6):463–471

    PubMed  CAS  Google Scholar 

  41. Lankiewicz S et al (2008) Circulating tumour cells as a predictive factor for response to systemic chemotherapy in patients with advanced colorectal cancer. Mol Oncol 2(4):349–355

    PubMed  Google Scholar 

  42. Findeisen P et al (2008) Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients. Int J Oncol 33(5):1001–1010

    PubMed  CAS  Google Scholar 

  43. Gazzaniga P et al (2010) Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cell Mol Med 14(8):2073–2077

    PubMed  CAS  Google Scholar 

  44. Wong SC et al (2011) Clinical significance of CDX2-positive circulating tumour cells in colorectal cancer patients. Br J Cancer 104(6):1000–1006

    PubMed  CAS  Google Scholar 

  45. Xi L et al (2007) Optimal markers for real-time quantitative reverse transcription PCR detection of circulating tumor cells from melanoma, breast, colon, esophageal, head and neck, and lung cancers. Clin Chem 53(7):1206–1215

    PubMed  CAS  Google Scholar 

  46. Riethdorf S, Wikman H, Pantel K (2008) Review: biological relevance of disseminated tumor cells in cancer patients. Int J Cancer 123(9):1991–2006

    PubMed  CAS  Google Scholar 

  47. Klein CA et al (2002) Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 360(9334):683–689

    PubMed  CAS  Google Scholar 

  48. Stoecklein NH, Klein CA (2010) Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis. Int J Cancer 126(3):589–598

    PubMed  CAS  Google Scholar 

  49. Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9(4):302–312

    PubMed  CAS  Google Scholar 

  50. Weber JC et al (2007) Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes. Int J Cancer 120(3):524–532

    PubMed  CAS  Google Scholar 

  51. Conzelmann M, Linnemann U, Berger MR (2005) Molecular detection of clinical colorectal cancer metastasis: how should multiple markers be put to use? Int J Colorectal Dis 20(2):137–146

    PubMed  Google Scholar 

  52. Kraus MC, Linnemann U, Berger MR (2011) Disseminated colorectal tumor cells in organs prone to metastasis detected by new double enriched nested-PCR in comparison with recognized assays. Oncol Rep 25(5):1421–1429

    PubMed  CAS  Google Scholar 

  53. Tortola S et al (2001) Discordance between K-ras mutations in bone marrow micrometastases and the primary tumor in colorectal cancer. J Clin Oncol 19(11):2837–2843

    PubMed  CAS  Google Scholar 

  54. Braun S et al (2000) Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin Oncol 18(1):80–86

    PubMed  CAS  Google Scholar 

  55. Wikman H, Vessella R, Pantel K (2008) Cancer micrometastasis and tumour dormancy. APMIS 116(7–8):754–770

    PubMed  CAS  Google Scholar 

  56. Sosa MS et al (2011) ERK1/2 and p38alpha/beta signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin Cancer Res 17(18):5850–5857

    PubMed  CAS  Google Scholar 

  57. Alencar H et al (2005) A novel mouse model for segmental orthotopic colon cancer. Int J Cancer 117(3):335–339

    PubMed  CAS  Google Scholar 

  58. Bhullar JS et al (2011) A novel nonoperative orthotopic colorectal cancer murine model using electrocoagulation. J Am Coll Surg 213(1):54–60, discussion 60–1

    PubMed  Google Scholar 

  59. Bresalier RS et al (1987) An animal model for colon cancer metastasis: establishment and characterization of murine cell lines with enhanced liver-metastasizing ability. Cancer Res 47(5):1398–1406

    PubMed  CAS  Google Scholar 

  60. Donigan M et al (2010) A metastatic colon cancer model using nonoperative transanal rectal injection. Surg Endosc 24(3):642–647

    PubMed  Google Scholar 

  61. Eliane JP et al (2008) Monitoring serial changes in circulating human breast cancer cells in murine xenograft models. Cancer Res 68(14):5529–5532

    PubMed  CAS  Google Scholar 

  62. Fu XY et al (1991) Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. Proc Natl Acad Sci U S A 88(20):9345–9349

    PubMed  CAS  Google Scholar 

  63. Galanzha EI et al (2009) In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser. Cancer Res 69(20):7926–7934

    PubMed  CAS  Google Scholar 

  64. Kolostova K et al (2011) Circulating human prostate cancer cells from an orthotopic mouse model rapidly captured by immunomagnetic beads and imaged by GFP expression. Anticancer Res 31(5):1535–1539

    PubMed  CAS  Google Scholar 

  65. Lupu CM et al (2006) An orthotopic colon cancer model for studying the B7-H3 antitumor effect in vivo. J Gastrointest Surg 10(5):635–645

    PubMed  Google Scholar 

  66. Zigmond E et al (2011) Utilization of murine colonoscopy for orthotopic implantation of colorectal cancer. PLoS One 6(12):e28858

    PubMed  CAS  Google Scholar 

  67. Peach G et al (2010) Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer 102(9):1327–1334

    PubMed  CAS  Google Scholar 

  68. Rahbari NN et al (2010) Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology 138(5):1714–1726

    PubMed  Google Scholar 

  69. Weitz J et al (1998) Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res 4(2):343–348

    PubMed  CAS  Google Scholar 

  70. Bessa X et al (2001) Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer. Gastroenterology 120(5):1084–1092

    PubMed  CAS  Google Scholar 

  71. Bessa X et al (2003) Prognostic value of postoperative detection of blood circulating tumor cells in patients with colorectal cancer operated on for cure. Ann Surg 237(3):368–375

    PubMed  Google Scholar 

  72. Bosch B et al (2003) Perioperative detection of disseminated tumour cells is an independent prognostic factor in patients with colorectal cancer. Br J Surg 90(7):882–888

    PubMed  CAS  Google Scholar 

  73. Koch M et al (2005) Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases. Ann Surg 241(2):199–205

    PubMed  Google Scholar 

  74. Allen-Mersh TG et al (2007) Role of circulating tumour cells in predicting recurrence after excision of primary colorectal carcinoma. Br J Surg 94(1):96–105

    PubMed  CAS  Google Scholar 

  75. Koyanagi K et al (2008) Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial. Clin Cancer Res 14(22):7391–7396

    PubMed  CAS  Google Scholar 

  76. Uen YH et al (2008) Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I–III colorectal cancer after curative resection. Ann Surg Oncol 15(8):2120–2128

    PubMed  Google Scholar 

  77. Allard WJ et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10(20):6897–6904

    PubMed  Google Scholar 

  78. Negin BP, Cohen SJ (2010) Circulating tumor cells in colorectal cancer: past, present, and future challenges. Curr Treat Options Oncol 11(1–2):1–13

    PubMed  Google Scholar 

  79. Cohen SJ et al (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26(19):3213–3221

    PubMed  Google Scholar 

  80. Cohen SJ et al (2009) Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol 20(7):1223–1229

    PubMed  CAS  Google Scholar 

  81. Tol J et al (2008) A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol 19(4):734–738

    PubMed  CAS  Google Scholar 

  82. Wong SC et al (2009) Clinical significance of cytokeratin 20-positive circulating tumor cells detected by a refined immunomagnetic enrichment assay in colorectal cancer patients. Clin Cancer Res 15(3):1005–1012

    PubMed  CAS  Google Scholar 

  83. Lindemann F et al (1992) Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet 340(8821):685–689

    PubMed  CAS  Google Scholar 

  84. Pantel K et al (1996) Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases. Lancet 347(9002):649–653

    PubMed  CAS  Google Scholar 

  85. Leinung S et al (2000) Cytokeratin-positive cells in bone marrow in comparison with other prognostic factors in colon carcinoma. Langenbecks Arch Surg 385(5):337–343

    PubMed  CAS  Google Scholar 

  86. Broll R et al (1996) Tumor cell dissemination in bone marrow and peritoneal cavity. An immunocytochemical study of patients with stomach or colorectal carcinoma. Langenbecks Arch Chir 381(1):51–58

    PubMed  CAS  Google Scholar 

  87. Cohen AM et al (1998) In vitro detection of occult bone marrow metastases in patients with colorectal cancer hepatic metastases. Dis Colon Rectum 41(9):1112–1115

    PubMed  CAS  Google Scholar 

  88. Juhl H et al (1994) Immunocytological detection of micrometastatic cells: comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric, colorectal and pancreatic cancer patients. Int J Cancer 57(3):330–335

    PubMed  CAS  Google Scholar 

  89. Schott A et al (1998) Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker. Ann Surg 227(3):372–379

    PubMed  CAS  Google Scholar 

  90. Flatmark K et al (2002) Immunomagnetic detection of micrometastatic cells in bone marrow of colorectal cancer patients. Clin Cancer Res 8(2):444–449

    PubMed  Google Scholar 

  91. Pantel K et al (1994) Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J Hematother 3(3):165–173

    PubMed  CAS  Google Scholar 

  92. Schoppmeyer K et al (2006) Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases. Oncol Rep 15(2):449–454

    PubMed  CAS  Google Scholar 

  93. O’Sullivan GC et al (1997) Micrometastases: marker of metastatic potential or evidence of residual disease? Gut 40(4):512–515

    PubMed  Google Scholar 

  94. Leinung S et al (2000) Detection of cytokeratin-positive cells in bone marrow in breast cancer and colorectal carcinoma in comparison with other factors of prognosis. J Hematother Stem Cell Res 9(6):905–911

    PubMed  CAS  Google Scholar 

  95. Vlems FA et al (2003) Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer. Br J Surg 90(8):989–995

    PubMed  CAS  Google Scholar 

  96. Soeth E et al (1996) The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of disease. Int J Cancer 69(4):278–282

    PubMed  CAS  Google Scholar 

  97. Soeth E et al (1997) Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR. Cancer Res 57(15):3106–3110

    PubMed  CAS  Google Scholar 

  98. Gerhard M et al (1994) Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction. J Clin Oncol 12(4):725–729

    PubMed  CAS  Google Scholar 

  99. Conzelmann M et al (2003) Cytokeratin 20 and guanylyl cyclase C mRNA is largely present in lymph node and liver specimens of colorectal cancer patients. Int J Cancer 107(4):617–628

    PubMed  CAS  Google Scholar 

  100. Ausch C et al (2009) Circulating cytokeratin 18 fragment m65-a potential marker of malignancy in colorectal cancer patients. J Gastrointest Surg 13(11):2020–2026

    PubMed  Google Scholar 

  101. Buergy D et al (2009) Prognostic impact of extracellular matrix metalloprotease inducer: immunohistochemical analyses of colorectal tumors and immunocytochemical screening of disseminated tumor cells in bone marrow from patients with gastrointestinal cancer. Cancer 115(20):4667–4678

    PubMed  CAS  Google Scholar 

  102. Vogelaar FJ et al (2010) Clinical impact of different detection methods for disseminated tumor cells in bone marrow of patients undergoing surgical resection of colorectal liver metastases: a prospective follow-up study. BMC Cancer 10:153

    PubMed  Google Scholar 

  103. Buxhofer-Ausch V et al (2010) Spontaneous changes in tumour cell dissemination to bone marrow in colorectal cancer. Colorectal Dis 12(8):776–782

    PubMed  CAS  Google Scholar 

  104. Valladares-Ayerbes M et al (2011) Prognostic impact of disseminated tumor cells and microRNA-17-92 cluster deregulation in gastrointestinal cancer. Int J Oncol 39(5):1253–1264

    PubMed  Google Scholar 

  105. Greenson JK et al (1994) Identification of occult micrometastases in pericolic lymph nodes of Duke’s B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49. Correlation with long-term survival. Cancer 73(3):563–569

    PubMed  CAS  Google Scholar 

  106. Nakanishi Y et al (1999) Clinical implications of lymph node micrometastases in patients with colorectal cancers. A case control study. Oncology 57(4):276–280

    PubMed  CAS  Google Scholar 

  107. Oberg A et al (1998) Are lymph node micrometastases of any clinical significance in Dukes stages A and B colorectal cancer? Dis Colon Rectum 41(10):1244–1249

    PubMed  CAS  Google Scholar 

  108. Weitz J et al (1999) Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow. Clin Cancer Res 5(7):1830–1836

    PubMed  CAS  Google Scholar 

  109. Rosenberg R et al (2004) Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer. Int J Colorectal Dis 19(5):430–437

    PubMed  Google Scholar 

  110. Conzelmann M, Linnemann U, Berger MR (2004) K-ras codon 12 and 13 mutations are correlated with differential patterns of tumor cell dissemination in colorectal cancer patients. Int J Oncol 24(6):1537–1544

    PubMed  CAS  Google Scholar 

  111. Rahbari NN, et al. (2012) Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. doi:10.1200/JCO.2011.36.9504

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Gunnar Steinert, Sebastian Schölch, Moritz Koch & Jürgen Weitz

Authors
  1. Gunnar Steinert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastian Schölch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Moritz Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jürgen Weitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jürgen Weitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steinert, G., Schölch, S., Koch, M. et al. Biology and significance of circulating and disseminated tumour cells in colorectal cancer. Langenbecks Arch Surg 397, 535–542 (2012). https://doi.org/10.1007/s00423-012-0917-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-012-0917-9

Keywords

Search

Navigation