Detection of micrometastatic disease and monitoring of perioperative tumor cell dissemination in primary operable breast cancer patients using real-time quantitative reverse transcription-PCR.
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.
Ismail
Mohamed Saad
MS
Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium and National Cancer Institute, Cairo, Egypt.
Wynendaele
Wim
W
Aerts
Joeri L E
JL
Paridaens
Robert
R
Gaafar
Rabab
R
Shakankiry
Nayera
N
Khaled
Hussein M
HM
Christiaens
Marie-Rose
MR
Wildiers
Hans
H
Omar
Sherif
S
Vandekerckhove
Philippe
P
Van Oosterom
Allan T
AT
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
D014408:Biomarkers, Tumor; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007633:Keratins