title: Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes' stage B and C colorectal cancer.
abstract: OBJECTIVE
  Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery.
  
  
  METHODS
  In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n = 420) or prospective validation set (n = 315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay.
  
  
  RESULTS
  In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer.
  
  
  CONCLUSIONS
  In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-0003, Japan. iinuma@med.teikyo-u.ac.jp
authors.forename: Hisae
authors.initials: H
authors.lastname: Iinuma
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Miki
authors.initials: M
authors.lastname: Adachi
authors.forename: Naoko
authors.initials: N
authors.lastname: Hayashi
authors.forename: Junko
authors.initials: J
authors.lastname: Tamura
authors.forename: Keiji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fukushima
authors.forename: Kota
authors.initials: K
authors.lastname: Okinaga
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sasako
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000235:genetics; D053554:Keratin-20 / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D018579:Patient Selection; D010455:Peptides / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; C507499:KRT20 protein, human; D053539:Keratin-19; D053554:Keratin-20; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger