title: Detection of epithelial messenger RNA in the plasma of breast cancer patients is associated with poor prognosis tumor characteristics.
abstract: OBJECTIVE
  Free plasma RNA has been scarcely studied in patients with cancer. Here we examine the presence of RNA from epithelial tumors in plasma from a series of breast cancer patients and its correlation with tumor characteristics and circulating tumor cells.
  
  
  METHODS
  beta-actin mRNA was analyzed to check the viability of plasma RNA in samples from 45 patients with breast cancer and 25 controls. Nested primers were used to detect the presence of cytokeratin 19 (CK19) and Mammaglobin in the same samples. Eleven clinicopathological parameters were studied and correlated with molecular parameters. Additionally, we looked for circulating tumor cells in 16 of these patients and in 10 of the controls.
  
  
  RESULTS
  All samples showed detectable quantities of beta-actin RNA. In controls, 3 cases (12%) were positive for Mammaglobin, and 5 (20%) were positive for CK19 RNA; of the 45 patients, 27 cases (60%) were positive for Mammaglobin, and 22 (49%) were positive for CK19. These differences were statistically significant (P = 0.001). Tumor size (P = 0.01) and proliferative index (P = 0.02) were associated with the presence of Mammaglobin, CK19, or both RNAs in plasma. Pathological stage (P = 0.06) was close to significance. Although a statistical relationship was not demonstrated, 9 of the 10 patients with circulating tumor cells showed epithelial mRNAs in plasma.
  
  
  CONCLUSIONS
  We conclude that epithelial tumor RNA is detectable in plasma from breast cancer patients and that this finding is associated with a probable poor prognosis and circulating tumor cells.
authors.affiliation: Department of Medical Oncology, Clinica Puerta de Hierro, E-28035 Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Silva
authors.forename: G
authors.initials: G
authors.lastname: Dominguez
authors.forename: J
authors.initials: J
authors.lastname: Silva
authors.forename: J M
authors.initials: JM
authors.lastname: Garcia
authors.forename: A
authors.initials: A
authors.lastname: Sanchez
authors.forename: O
authors.initials: O
authors.lastname: Rodriguez
authors.forename: M
authors.initials: M
authors.lastname: Provencio
authors.forename: P
authors.initials: P
authors.lastname: España
authors.forename: F
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D000199:Actins / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000235:genetics; D060785:Mammaglobin A; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014598:Uteroglobin / Q000235:genetics
chemical_list: D000199:Actins; D060785:Mammaglobin A; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C556448:SCGB2A2 protein, human; D007633:Keratins; D014598:Uteroglobin