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Originally published as JCO Early Release 10.1200/JCO.2005.04.5948 on June 12 2006

Journal of Clinical Oncology, Vol 24, No 23 (August 10), 2006: pp. 3756-3762
© 2006 American Society of Clinical Oncology.

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Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells Detected by Real-Time Polymerase Chain Reaction in Node-Negative Breast Cancer Patients

Nikos Xenidis, Maria Perraki, Maria Kafousi, Stella Apostolaki, Irene Bolonaki, Aliki Stathopoulou, Kostas Kalbakis, Nikos Androulakis, Charalambos Kouroussis, Thanos Pallis, Charalambos Christophylakis, Katerina Argyraki, Evi S. Lianidou, Stathis Stathopoulos, Vassilis Georgoulias, Dimitris Mavroudis

From the Departments of Medical Oncology Pathology, University General Hospital of Heraklion; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete; and the Laboratory of Analytical Chemistry, Faculty of Chemistry, University of Athens, Athens, Greece.

Address reprint requests to Vassilis Georgoulias, MD, PhD, Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, 711 10 Heraklion, Crete, Greece; e-mail: georgsec{at}med.uoc.gr

Purpose: To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node–negative breast cancer patients.

Patients and Methods: Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated.

Results: CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008).

Conclusion: Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.

published online ahead of print at www.jco.org on June 12, 2006.

Supported in part by research grants from the Cretan Association of Biomedical Research (CABR). A.S and A.P were recipients of a CABR research fellowship.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.




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