title: Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhong Shan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, People's Republic of China.
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Sun
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology; D055028:Comparative Genomic Hybridization / Q000379:methods; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007680:Kidney Neoplasms / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000276:immunology* / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor