FCCC LOGO Faculty Publications
Cohen SJ , Alpaugh RK , Gross S , O'Hara SM , Smirnov DA , Ferstappen Lwmm , Allard WJ , Bilbee M , Cheng JD , Hoffman JP , Lewis NL , Pellegrino A , Rogatko A , Sigurdson E , Wang H , Watson JC , Weiner LM , Meropol NJ
Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer
Clinical Colorectal Cancer. 2006 Jul;6(2) :125-132
PMID: ISI:000242172000004   
Back to previous list
Abstract
Purpose: Development of targeted therapeutic agents in colorectal cancer (CRC) is impeded by the lack of a noninvasive surrogate of drug effect. This pilot study evaluated the ability of immunomagnetic separation to isolate circulating tumor cells (CTCs) and of the fluorescent microscope system and flow cytometry to enumerate and characterize CTCs from patients with metastatic CRC. Patients and Methods: Fifty patients with metastatic CRC contributed 50 mL of blood at treatment initiation and disease evaluation timepoints. Fresh tumor specimens were obtained from 17 patients for comparison of circulating and in situ tumor cell characteristics. Epithelial cells were magnetically isolated from whole blood targeting the antiepithelial cell adhesion molecule (EpCAM). Circulating tumor cells were defined as EpCAM isolated, cytokeratin positive, nuclear stain positive, and CD45 negative. Total RNA was isolated from EpCAM-enriched CTCs and multigene reverse-transcriptase polymerase chain reaction analyses were performed. Results: The median number of CTCs detected by flow cytometry was 2/7.5 mL blood. Mean change in cell count was significantly different for patients with tumor progression versus nonprogression (+6.7 vs. +0.2/7.5 mL; P = 0.001). A correlation was noted between mean fluorescence intensity (flow cytometry) of cytokeratin in CTC and matched tumor specimens (r = 0.79, P = 0.06). Nearly 80% (15 of 19) of samples with >= 2 CTCs expressed >= 1 epithelial marker gene (CK19, CK20, carcinoembryonic antigen, or epidermal growth factor receptor). Conclusion: Isolating and characterizing CTCs from patients with metastatic CRC is feasible. Change in the CTC number might reflect clinical status, and flow cytometric and gene expression data suggest similarity of circulating and in situ tumor cells. Further evaluation of CTCs for pharmacodynamic and clinical monitoring in patients with CRC is warranted.
Notes
ISI Document Delivery No.: 107LB Times Cited: 0 Cited Reference Count: 23 Cited References: ALLARD WJ, 2004, CLIN CANCER RES, V10, P6897 BRAUN S, 2000, NEW ENGL J MED, V342, P525 CRISTOFANILLI M, 2004, NEW ENGL J MED, V351, P781 CUNNINGHAM D, 2004, NEW ENGL J MED, V351, P337 GOLDBERG RM, 2004, J CLIN ONCOL, V22, P23 HURWITZ H, 2004, NEW ENGL J MED, V350, P2335 JEMAL A, 2006, CA-CANCER J CLIN, V56, P106 KAPLAN EL, 1958, J AM STAT ASSOC, V53, P547 KEMENY N, 2001, LANCET ONCOL, V2, P418 KOCH M, 2001, ARCH SURG-CHICAGO, V136, P85 MEROPOL NJ, 2005, J CLIN ONCOL, V23, P1791 MOERTEL CG, 1990, NEW ENGL J MED, V322, P352 MORENO JG, 2001, UROLOGY, V58, P386 OHARA SM, 2004, CLIN CHEM, V50, P826 RACILA E, 1998, P NATL ACAD SCI USA, V95, P4589 SCARTOZZI M, 2004, J CLIN ONCOL, V22, P4772 SHIA J, 2005, MODERN PATHOL, V18, P1350 SUNDERMEYER ML, 2005, CLIN COLORECTAL CANC, V5, P108 THERASSE P, 2000, J NATL CANCER I, V92, P205 THIRION P, 2004, J CLIN ONCOL, V22, P3766 WECKERMANN D, 1999, J CLIN ONCOL, V17, P3438 WEINER LM, 2005, J CLIN ONCOL S 1, V23, S206 WHARTON RQ, 1999, CLIN CANCER RES, V5, P4158