Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

J Cancer Res Clin Oncol. 2011 Aug;137(8):1151-73. doi: 10.1007/s00432-011-0988-y. Epub 2011 Jun 17.


Background: Circulating tumor cells (CTCs) have long been considered a reflection of tumor aggressiveness. Hematogenous spreading of CTCs from a primary tumor is a crucial step in the metastasis cascade, which leads ultimately to the formation of overt metastases. However, owing to the rarity of CTCs in peripheral blood, detecting these cells requires methods combined with high sensitivity and specificity, which sets tremendous challenges for the implementation of these assays into clinical routine.

Methods: Generally, CTCs detection methods are composed of the following two steps: enrichment (isolation) process (morphological and immunological techniques) and detection (identification) process (cytometric and nucleic acid techniques), which may or may not be separate from enrichment. Genetic and molecular characterization of CTCs carried out by fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH), PCR-based techniques, and biomarker immunofluorescent staining extract more information about malignant profile, metastatic potential of CTCs, and the extent to which CTCs are genetically identical to the primary tumor.

Results: Recent technical advances made it possible to detect CTCs. The efficacy of circulating tumor cell (CTC) detection among patients with solid malignancy has been investigated, which shows great potential to become a tool for real-time parameter of prognosis and serve as an early marker to assess the therapeutic response in overt cancers. Improvements in detection and characterization of CTCs will hopefully lead to refinement of clinical management of cancer patients.

Conclusion: This review addresses the majority of assays that have been published thus far, including the enrichment and detection steps and the markers used in these assays, accompanied by some biological issues of CTC and the results of clinical application harvested.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / pathology
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / pathology
  • Colorectal Neoplasms / pathology
  • Comparative Genomic Hybridization* / methods
  • Epithelial Cells / pathology
  • Female
  • Flow Cytometry / methods
  • Humans
  • In Situ Hybridization, Fluorescence* / methods
  • Kidney Neoplasms / pathology
  • Liver Neoplasms / pathology
  • Lung Neoplasms / pathology
  • Male
  • Mesenchymal Stem Cells / pathology
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / pathology
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Neoplastic Cells, Circulating / immunology*
  • Neoplastic Cells, Circulating / pathology*
  • Polymerase Chain Reaction* / methods
  • Prostatic Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / pathology
  • Urinary Bladder Neoplasms / pathology


  • Biomarkers, Tumor