title: Detection of micrometastatic disease and monitoring of perioperative tumor cell dissemination in primary operable breast cancer patients using real-time quantitative reverse transcription-PCR.
abstract: OBJECTIVE
  We previously found a statistically significant number of cytokeratin 19 (CK19)+ cells in peripheral blood (PB) of stage IV breast cancer (BC) patients compared with those of healthy volunteers, using a quantitative real-time reverse transcription-PCR. We aimed to apply the technique on bone marrow (BM) of primary operable BC patients. Pre- and postoperative PB samples of these patients were further analyzed to investigate possible shedding of CK19+ cells during the operation.
  
  
  METHODS
  In 54 primary operable BC patients, we analyzed 50 BM samples taken preoperatively and 297 PB samples. PB samples were collected before surgery; immediately after surgery; on the first, second, and fifth day postoperatively; and one month postoperatively.
  
  
  RESULTS
  In BM of controls and BC patients, we detected a median of 28 and 568 CK19+ cells/5 x 10(6) leukocytes, respectively (P < 0.001). In preoperative blood (B-1) samples, we measured a median of 109 CK19+ cells. Using the upper limit of 95% confidence interval of controls as cutoff, 74% and 52% of BM and (B-1), respectively were considered CK19+. There was no significant correlation between CK19+ cells in BM and (B-1) and classical prognostic factors. We found no significant difference between blood samples at different time points with respect to the average CK19+ cells.
  
  
  CONCLUSIONS
  In primary BC patients, we detected high numbers of CK19+ cells in BM and PB (B-1) samples compared with controls. However, no significant correlation between the presence of CK19+ cells in BM and PB and classical prognostic factors was found. We detected no statistically significant influence of surgical manipulation on CK19+ cells.
authors.affiliation: Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium and National Cancer Institute, Cairo, Egypt.
authors.forename: Mohamed Saad
authors.initials: MS
authors.lastname: Ismail
authors.forename: Wim
authors.initials: W
authors.lastname: Wynendaele
authors.forename: Joeri L E
authors.initials: JL
authors.lastname: Aerts
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Rabab
authors.initials: R
authors.lastname: Gaafar
authors.forename: Nayera
authors.initials: N
authors.lastname: Shakankiry
authors.forename: Hussein M
authors.initials: HM
authors.lastname: Khaled
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Christiaens
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
authors.forename: Sherif
authors.initials: S
authors.lastname: Omar
authors.forename: Philippe
authors.initials: P
authors.lastname: Vandekerckhove
authors.forename: Allan T
authors.initials: AT
authors.lastname: Van Oosterom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D017931:DNA Primers; D005260:Female; D006801:Humans; D007633:Keratins / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011184:Postoperative Period; D011300:Preoperative Care; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D012334:RNA, Neoplasm / Q000097:blood; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007633:Keratins