title: Molecular detection and prognostic value of circulating cytokeratin-19 messenger RNA-positive and HER2 messenger RNA-positive cells in the peripheral blood of women with early-stage breast cancer.
abstract: OBJECTIVE
  The aim of this study was to evaluate the clinical relevance of the simultaneous detection of cytokeratin (CK)-19 messenger RNA (mRNA)- and HER2 mRNA-positive cells in peripheral blood of women with early-stage breast cancer.
  
  
  METHODS
  CK-19 mRNA- and HER2 mRNA-positive cells were detected using a real-time and a nested reverse-transcriptase polymerase chain reaction assay, respectively, in a cohort of 185 women with early-stage breast cancer before the initiation of any adjuvant systemic treatment. Detection of CK-19 mRNA- and HER2 mRNA-positive cells in the peripheral blood was correlated with clinical outcome.
  
  
  RESULTS
  Overall, 63 of the 185 patients (34%) had detectable CK-19 mRNA-positive cells, and 33 (52.3%) also had detectable HER2 mRNA-positive cells. Patients with CK-19/HER2 mRNA-negative cells showed a trend toward longer disease-free survival (DFS) compared with patients with CK-19 mRNA-positive/HER2 mRNA-negative cells (P = .054) and had longer DFS than patients with CK-19/HER2 mRNA-positive cells (P < .001). Similarly, overall survival (OS) was higher in patients with CK-19/HER2 mRNA-negative cells compared with patients with CK-19 mRNA-positive/HER2 mRNA-negative cells (P = .039) or CK-19/HER2 mRNA-positive cells (P < .001). Patients with CK-19/HER2 mRNA-positive cells had shorter DFS but not OS compared with patients with CK-19 mRNA-positive/HER2 mRNA-negative cells. In multivariate analysis, the simultaneous detection of CK-19 mRNA- and HER2 mRNA-positive cells was independently associated with early relapse.
  
  
  CONCLUSIONS
  The simultaneous detection of CK-19 mRNA- and HER2 mRNA-positive cells in peripheral blood predicts poor clinical outcome for women with early-stage breast cancer.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion,Crete, Greece.
authors.forename: Michail
authors.initials: M
authors.lastname: Ignatiadis
authors.forename: Maria
authors.initials: M
authors.lastname: Perraki
authors.forename: Stella
authors.initials: S
authors.lastname: Apostolaki
authors.forename: Eleni
authors.initials: E
authors.lastname: Politaki
authors.forename: Nikos
authors.initials: N
authors.lastname: Xenidis
authors.forename: Maria
authors.initials: M
authors.lastname: Kafousi
authors.forename: Efstathios
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: Evi
authors.initials: E
authors.lastname: Lianidou
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D011960:Receptors, Estrogen / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human