Detection of Micrometastatic Disease and Monitoring of Perioperative Tumor Cell Dissemination in Primary Operable Breast Cancer Patients Using Real-Time Quantitative Reverse Transcription-PCR

• Published in: Clinical cancer research 2004-01, Vol.10 (1), p.196-201
• Main Authors: SAAD ISMAIL, Mohamed, WYNENDAELE, Wim, VANDEKERCKHOVE, Philippe, VAN OOSTEROM, Allan T, AERTS, Joeri L. E, PARIDAENS, Robert, GAAFAR, Rabab, SHAKANKIRY, Nayera, KHALED, Hussein M, CHRISTIAENS, Marie-Rose, WILDIERS, Hans, OMAR, Sherif
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - genetics; Bone Marrow Cells - metabolism; Breast Neoplasms - blood; Breast Neoplasms - diagnosis; Breast Neoplasms - surgery; DNA Primers; Female; Humans; Keratins - genetics; Medical sciences; Middle Aged; Neoplasm Metastasis; Pharmacology. Drug treatments; Postoperative Period; Preoperative Care; Prognosis; RNA, Messenger - blood; RNA, Neoplasm - blood; Tumor Cells, Cultured; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-0515-2

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 × 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.