Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases

Clinical Cancer Research - Tập 10 Số 20 - Trang 6897-6904 - 2004
W. Jeffrey Allard1, Jeri Matera1, Michael Craig Miller1, Madeline Repollet1, Mark C. Connelly1, Chinthalapally V. Rao1, Arjan G.J. Tibbe1, Jonathan W. Uhr2,3, Leon W.M.M. Terstappen1
11Immunicon Corporation, Huntingdon Valley, Pennsylvania; and
22Cancer Immunobiology Center and Departments of Microbiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
3Immunology

Tóm tắt

Abstract Purpose: The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. Experimental Design: The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Results: Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of ≥85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had ≥2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 ± 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had ≥2 CTCs. Detection of ≥2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. Conclusions: The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.

Từ khóa


Tài liệu tham khảo

Racila E, Euhus D, Weiss AJ, et al Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci USA 1998;95:4589-94.

Gomella LG, Raj GV, Moreno JG. Reverse transcriptase polymerase chain reaction for prostate specific antigen in the management of prostate cancer. J Urol 1997;158:326-37.

Ghossein RA, Bhattacharya S, Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin Cancer Res 1999;5:1950-60.

Jiang WG, Martin TA, Mansel RE. Molecular detection of micro-metastasis in breast cancer. Crit Rev Oncol Hematol 2002;43:13-31.

Gaforio JJ, Serrano MJ, Sanchez-Rovira P, et al Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis. Int J Cancer 2003;107:984-90.

Brugger W, Bross K, Glatt M, et al Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. Blood 1994;83:636-40.

Ross AA, Cooper BW, Lazarus HM, et al Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunohistochemical and clonogenic assay techniques. Blood 1993;82:2605-10.

Moss TJ, To LB, Pantel K. Evaluation of grafts for occult tumor cells. J Hematother 1994;3:163-4.

Molnar B, Ladanyi A, Tanko L, Sréter L, Tulassay Z. Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin Cancer Res 2001;7:4080-5.

Witzig TE, Bossy B, Kimlinger T, et al Detection of circulating cytokeratin-positive cells in the blood of breast cancer patients using immunomagnetic enrichment and digital microscopy. Clin Cancer Res 2002;8:1085-91.

Wang Z, Eisenberger MA, Carducci MA, et al Identification and characterization of circulating prostate carcinoma cells. Cancer (Phila) 2000;88:2787-95.

Méhes G, Witt A, Kubista E, Ambros PF. Circulating breast cancer cells are frequently apoptotic. Am J Pathol 2001;159:17-20.

Moreno JG, O’Hara SM, Gross S, et al Changes in circulating carcinoma cells in metastatic prostate cancer patients correlates with disease status. Urology 2001;58:386-92.

Soria JC, Gauthier LR, Raymond E, et al Molecular detection of telomerase positive circulating epithelial cells in metastatic breast cancer patients. Clin Cancer Res 1999;5:971-5.

Pierga JY, Bonneton C, Vincent-Salomon A, et al Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast patients. Clin Cancer Res 2004;10:1392-400.

Fehm T, Sagalowsky A, Clifford E, et al Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res 2002;8:2073-84.

Hayes DF, Walker TM, Singh B, et al Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int J Oncol 2002;21:1111-8.

O’Hara SM, Moreno JG, Zweitzig DR, et al Multigene reverse transcription-PCR profiling of circulating tumor cells in hormone-refractory prostate cancer. Clin Chem 2004;50:826-35.

Naume B, Borgen E, Beiske K, et al Immunomagnetic techniques for the enrichment and detection of isolated breast carcinoma cells in bone marrow and peripheral blood. J Hematother 1997;6:103-14.

Hardingham JE, Kotasek D, Farmer B, et al Immunobead-PCR: a technique for the detection of circulating tumor cells using immunomagnetic beads and the polymerase chain reaction. Cancer Res 1993;53:3455-8.

Zigeuner RE, Riesenberg R, Pohla H, Hofstetter A, Oberneder R. Immunomagnetic cell enrichment detects more disseminated cancer cells than immunocytochemistry in vitro. J Urol 2000;164:1834-7.

Bilkenroth U, Taubert H, Riemann D, et al Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation. Int J Cancer 2001;92:577-82.

Kagan M, Howard D, Bendele T, et al A sample preparation and analysis system for identification of circulating tumor cells. J Clin Ligand Assay 2002;25:104-10.

Rao C, Rutner H, Hermann M, Russell T, Terstappen LWMM. Preservation of blood specimens to prevent breakdown of circulating tumor cells. Proc Am Assoc Cancer Res 2002;43:734

Allard WJ, Hayes DF, Repollet MI, et al A cellular preservative improves the specificity and yield of circulating tumor cells in carcinoma patients[abstract A3482]. Proc Am Soc Clin Oncol 2003;22:866

Cristofanilli M, Budd GT, Ellis MJ, et al Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004;351:781-91.

Kagan M, Howard D, Bendele T, et al Circulating tumor cells as cancer markers, a sample preparation and analysis system Diamandis EP Fritsche HA Lilja H Chan DW Schwartz M eds. . Tumor markers: physiology, pathobiology, technology and clinical applications 2002p. 495-8. AACC Press Washington, DC

Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium specific surface glycoprotein in normal and malignant tissues. Cancer Res 1987;47:2883-91.

National Committee for Clinical Laboratory Standards. Evaluation of precision performance of clinical chemistry devices; Approved guideline. National Committee for Clinical Laboratory Standards document EP-5A; ISBN 1-56238-368X; 1999.

Motulsky H. The confidence interval of counted variables. Intuitive biostatistics 1995p. 245-9. Oxford University Press New York

Box GEP, Hunter WG, Hunter JS. Significance tests and confidence intervals for means, variances, proportions, and frequencies Bradley RA Hunter JS Kendall DG Watson GS eds. . Statistics for experimenters 1978p. 137-45. John Wiley and Sons New York

Liberti PA, Rao CG, Terstappen LWMM. Optimization of ferrofluids and protocols for the enrichment of breast tumor cells in blood. J Magnetism Magnetic Materials 2001;225:301-7.

Borgen E, Naume B, Nesland JM, et al Standardization of the immunocytochemical detection of cancer cells in BM and blood. I. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1999;5:377-88.

Larson CJ, Moreno JG, Pienta KJ, et al. Apoptosis of circulating tumor cells in prostate cancer patients. Cytometry. In press 2004.

Gao CL, Rawal SK, Sun L, et al Diagnostic potential of prostate-specific antigen expressing epithelial cells in blood of prostate cancer patients. Clin Cancer Res 2003;9:2545-50.

Ellis WJ, Pfitzenmaier J, Colli J, et al Detection and isolation of prostate cancer cells from peripheral blood and bone marrow. Urology 2003;61:277-81.

Miller MC, Gross S, Allard WJ, et al Circulating tumor cells (CTCs) predict survival in patients with metastatic prostate cancer[abstract A5270]. Proc Am Assoc Cancer Res 2004;45:1215

Cristofanilli M, Reuben JM, Fritsche HA, et al Circulating tumor cells (CTCs): a novel prognostic factor for newly diagnosed metastatic breast cancer (MBC)[abstract A1349]. Proc Am Assoc Cancer Res 2003;44:1349

Thông tin
Thông tin xuất bản

Clinical Cancer Research

Tập 10 Số 20

6897-6904

Thông tin tác giả