title: Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer.
abstract: BACKGROUND
  To compare detection rates and evaluate the clinical relevance of cytokeratin-19 (CK-19) mRNA-positive cells in the peripheral blood (circulating tumour cells, CTCs) and bone marrow (disseminated tumour cells; DTCs) of patients with early breast cancer.
  
  
  METHODS
  Paired samples of peripheral blood and bone marrow were obtained from 165 patients with stage I-II breast cancer before the initiation of adjuvant chemotherapy. In 84 patients, paired blood and bone marrow samples were also available after chemotherapy. The detection of CK-19 mRNA-positive CTCs and DTCs was assessed by real-time PCR.
  
  
  RESULTS
  CK-19 mRNA-positive CTCs and DTCs were detected in 55.2 and 57.6% of patients before chemotherapy, respectively. After chemotherapy, CTCs and DTCs were identified in 44 (52.4%) and 43 (51.2%) of the 84 patients, respectively. There was a 93.9% (McNemar; P=0.344) and 72.6% (McNemar; P=0.999) concordance between blood and bone marrow samples before and after chemotherapy, respectively. The detection of CK-19 mRNA-positive CTCs or DTCs before chemotherapy was associated with decreased overall survival (P=0.024 and P=0.015, respectively). In addition, their simultaneous detection was also associated with an increased incidence of disease-related death and decreased overall survival (P=0.016).
  
  
  CONCLUSIONS
  The detection of CK-19 mRNA-positive CTCs using reverse transcription-PCR (RT-PCR) both before and after chemotherapy is correlated with the detection of CK-19 mRNA-positive DTCs in patients with early-stage breast cancer. The determination of the CTC status by RT-PCR conveys clinically relevant information that is not inferior to DTC status and, owing to the ease of sampling, warrants further evaluation as a tool for monitoring minimal residual disease.
authors.affiliation: Department of Pathology, University General Hospital of Heraklion, Crete 71110, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Daskalaki
authors.forename: S
authors.initials: S
authors.lastname: Agelaki
authors.forename: M
authors.initials: M
authors.lastname: Perraki
authors.forename: S
authors.initials: S
authors.lastname: Apostolaki
authors.forename: N
authors.initials: N
authors.lastname: Xenidis
authors.forename: E
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: E
authors.initials: E
authors.lastname: Kontopodis
authors.forename: D
authors.initials: D
authors.lastname: Hatzidaki
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001853:Bone Marrow / Q000473:pathology; D019046:Bone Marrow Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000032:analysis / Q000378:metabolism*; D008408:Mastectomy; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011878:Radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053539:Keratin-19; D012333:RNA, Messenger