Detection of micrometastatic disease and monitoring of perioperative tumor cell dissemination in primary operable breast cancer patients using real-time quantitative reverse transcription-PCR

Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):196-201. doi: 10.1158/1078-0432.ccr-0515-2.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Bone Marrow Cells / metabolism
  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / surgery
  • DNA Primers
  • Female
  • Humans
  • Keratins / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Postoperative Period
  • Preoperative Care
  • Prognosis
  • RNA, Messenger / blood*
  • RNA, Neoplasm / blood
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • RNA, Messenger
  • RNA, Neoplasm
  • Keratins