This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taback, B. Articles by Hoon, D. S. B. Search for Related Content PubMed PubMed Citation Articles by Taback, B. Articles by Hoon, D. S. B.

Detection of Occult Metastatic Breast Cancer Cells in Blood by a Multimolecular Marker Assay

Correlation with Clinical Stage of Disease¹

Department of Molecular Oncology [B. T., A. D. C., C. T. K., P. J. B., D. S. B. H.] and the Joyce Eisenberg-Keefer Breast Center [A. E. G.], John Wayne Cancer Institute, Santa Monica, California 90404, and Department of Biomathematics, University of California Los Angeles School of Medicine, Los Angeles, California 90024 [H-J. W.]

Currently, molecular markers offer the unique opportunity to identify occult metastasis in early stage cancer patients not otherwise detected with conventional staging techniques. To date, well-characterized molecular tumor markers to detect occult breast cancer cells in blood are limited. Because breast tumors are heterogeneous in tumor marker expression, we developed a "multimarker" reverse transcription-PCR assay combined with the highly sensitive electrochemiluminescence automated detection system. Breast cancer cell lines (n = 7), primary breast tumors (n = 25), and blood from normal donors (n = 40) and breast cancer patients [n = 65; American Joint Committee on Cancer (AJCC) stages I-IV] were assessed for four mRNA tumor markers: ß-human chorionic gonadotropin (ß-hCG), oncogene receptor (c-Met), ß 14-N-acetylgalactosaminyl-transferase, and a tumor-associated antigen (MAGE-A3). None of the tumor markers were expressed in any normal donor bloods. Breast cancer cell lines and primary breast tumors expressed ß-hCG, c-Met, ß 14-N-acetylgalactosaminyl-transferase, and MAGE-A3 mRNA. Of the 65 breast cancer patient blood samples assessed, 2, 3, 15, 49, and 31% expressed 4, 3, 2, 1, and 0 of the mRNA tumor markers, respectively. At least two markers were expressed in 20% of the blood specimens. The addition of a combination of markers enhanced detection of systemic metastasis by 32%. In patient blood samples, the MAGE-A3 marker correlated significantly with tumor size (P = 0.0004) and AJCC stage (P = 0.007). The combination of ß-hCG and MAGE-A3 mRNA markers correlated significantly with tumor size (P = 0.04), and the marker combination c-Met and MAGE-A3 showed a significant correlation with tumor size (P = 0.005) as well as AJCC stage (P = 0.018). A multimarker reverse transcription-PCR assay that correlates with known clinicopathological prognostic parameters may have potential clinical utility by monitoring tumor progression with a blood test.

This article has been cited by other articles:

				D. Lopez, M. Sekharam, D. Coppola, and W. B. Carter Purified human chorionic gonadotropin induces apoptosis in breast cancer Mol. Cancer Ther., September 1, 2008; 7(9): 2837 - 2844. [Abstract] [Full Text] [PDF]

				L. Harris, H. Fritsche, R. Mennel, L. Norton, P. Ravdin, S. Taube, M. R. Somerfield, D. F. Hayes, and R. C. Bast Jr American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer J. Clin. Oncol., November 20, 2007; 25(33): 5287 - 5312. [Abstract] [Full Text] [PDF]

				T. Nakagawa, S. R. Martinez, Y. Goto, K. Koyanagi, M. Kitago, T. Shingai, D. A. Elashoff, X. Ye, F. R. Singer, A. E. Giuliano, et al. Detection of Circulating Tumor Cells in Early-Stage Breast Cancer Metastasis to Axillary Lymph Nodes Clin. Cancer Res., July 15, 2007; 13(14): 4105 - 4110. [Abstract] [Full Text] [PDF]

				M. Lacroix Significance, detection and markers of disseminated breast cancer cells Endocr. Relat. Cancer, December 1, 2006; 13(4): 1033 - 1067. [Abstract] [Full Text] [PDF]

				S Abdul-Rasool, S H Kidson, E Panieri, D Dent, K Pillay, and G S Hanekom An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes. J. Clin. Pathol., March 1, 2006; 59(3): 289 - 297. [Abstract] [Full Text] [PDF]

				O. S. Bruland, H. Hoifodt, G. Saeter, S. Smeland, and O. Fodstad Hematogenous Micrometastases in Osteosarcoma Patients Clin. Cancer Res., July 1, 2005; 11(13): 4666 - 4673. [Abstract] [Full Text] [PDF]

				M. Shinozaki, D. S.B. Hoon, A. E. Giuliano, N. M. Hansen, H.-J. Wang, R. Turner, and B. Taback Distinct Hypermethylation Profile of Primary Breast Cancer Is Associated with Sentinel Lymph Node Metastasis Clin. Cancer Res., March 15, 2005; 11(6): 2156 - 2162. [Abstract] [Full Text] [PDF]

				Y.-P. Sher, J.-Y. Shih, P.-C. Yang, S. R. Roffler, Y.-W. Chu, C.-W. Wu, C.-L. Yu, and K. Peck Prognosis of Non-Small Cell Lung Cancer Patients by Detecting Circulating Cancer Cells in the Peripheral Blood with Multiple Marker Genes Clin. Cancer Res., January 1, 2005; 11(1): 173 - 179. [Abstract] [Full Text] [PDF]

				H. Pincas, M. R. Pingle, J. Huang, K. Lao, P. B. Paty, A. M. Friedman, and F. Barany High sensitivity EndoV mutation scanning through real-time ligase proofreading Nucleic Acids Res., October 28, 2004; 32(19): e148 - e148. [Abstract] [Full Text] [PDF]

				A M Gilbey, D Burnett, R E Coleman, and I Holen The detection of circulating breast cancer cells in blood J. Clin. Pathol., September 1, 2004; 57(9): 903 - 911. [Abstract] [Full Text] [PDF]

				H. E. Carlson, P. Kane, Z. M. Lei, X. Li, and C. V. Rao Presence of Luteinizing Hormone/Human Chorionic Gonadotropin Receptors in Male Breast Tissues J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4119 - 4123. [Abstract] [Full Text] [PDF]

				Z. Soriano and J. D. Pardee M34 Actin Regulatory Protein Is a Sensitive Diagnostic Marker for Early- and Late-Stage Mammary Carcinomas Clin. Cancer Res., July 1, 2004; 10(13): 4437 - 4443. [Abstract] [Full Text] [PDF]

				G. F. V. Woude, G. J. Kelloff, R. W. Ruddon, H.-M. Koo, C. C. Sigman, J. C. Barrett, R. W. Day, A. P. Dicker, R. S. Kerbel, D. R. Parkinson, et al. Reanalysis of Cancer Drugs: Old Drugs, New Tricks Clin. Cancer Res., June 1, 2004; 10(11): 3897 - 3907. [Full Text] [PDF]

				T. El-Hefnawy, S. Raja, L. Kelly, W. L. Bigbee, J. M. Kirkwood, J. D. Luketich, and T. E. Godfrey Characterization of Amplifiable, Circulating RNA in Plasma and Its Potential as a Tool for Cancer Diagnostics Clin. Chem., March 1, 2004; 50(3): 564 - 573. [Abstract] [Full Text] [PDF]

				K. Pantel, V. Muller, M. Auer, N. Nusser, N. Harbeck, and S. Braun Detection and Clinical Implications of Early Systemic Tumor Cell Dissemination in Breast Cancer Clin. Cancer Res., December 15, 2003; 9(17): 6326 - 6334. [Abstract] [Full Text] [PDF]

				C. T. Kuo, D. S.B. Hoon, H. Takeuchi, R. Turner, H.-J. Wang, D. L. Morton, and B. Taback Prediction of Disease Outcome in Melanoma Patients by Molecular Analysis of Paraffin-Embedded Sentinel Lymph Nodes J. Clin. Oncol., October 1, 2003; 21(19): 3566 - 3572. [Abstract] [Full Text] [PDF]

				N. C. Twine, J. A. Stover, B. Marshall, G. Dukart, M. Hidalgo, W. Stadler, T. Logan, J. Dutcher, G. Hudes, A. J. Dorner, et al. Disease-associated Expression Profiles in Peripheral Blood Mononuclear Cells from Patients with Advanced Renal Cell Carcinoma Cancer Res., September 15, 2003; 63(18): 6069 - 6075. [Abstract] [Full Text] [PDF]

				W. G. Jiang, D. Grimshaw, T. A. Martin, G. Davies, C. Parr, G. Watkins, J. Lane, R. Abounader, J. Laterra, and R. E. Mansel Reduction of Stromal Fibroblast-induced Mammary Tumor Growth, by Retroviral Ribozyme Transgenes to Hepatocyte Growth Factor/Scatter Factor and its Receptor, c-MET Clin. Cancer Res., September 15, 2003; 9(11): 4274 - 4281. [Abstract] [Full Text] [PDF]

				T. A. Martin, C. Parr, G. Davies, G. Watkins, J. Lane, K. Matsumoto, T. Nakamura, R. E. Mansel, and W. G. Jiang Growth and angiogenesis of human breast cancer in a nude mouse tumour model is reduced by NK4, a HGF/SF antagonist Carcinogenesis, August 1, 2003; 24(8): 1317 - 1323. [Abstract] [Full Text] [PDF]

				T. G. Lugo, S. Braun, R. J. Cote, K. Pantel, and V. Rusch Detection and Measurement of Occult Disease for the Prognosis of Solid Tumors J. Clin. Oncol., July 1, 2003; 21(13): 2609 - 2615. [Full Text] [PDF]

				J.-M. Costa, A. Benachi, M. Olivi, Y. Dumez, M. Vidaud, and E. Gautier Fetal Expressed Gene Analysis in Maternal Blood: A New Tool for Noninvasive Study of the Fetus Clin. Chem., June 1, 2003; 49(6): 981 - 983. [Full Text] [PDF]

				R. A. Wascher, K. T. Huynh, A. E. Giuliano, N. M. Hansen, F. R. Singer, D. Elashoff, and D. S. B. Hoon Stanniocalcin-1: A Novel Molecular Blood and Bone Marrow Marker for Human Breast Cancer Clin. Cancer Res., April 1, 2003; 9(4): 1427 - 1435. [Abstract] [Full Text] [PDF]