Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

• Published in: British journal of cancer Vol. 101; no. 4; pp. 589 - 597
• Main Authors: Daskalaki, A, Agelaki, S, Perraki, M, Apostolaki, S, Xenidis, N, Stathopoulos, E, Kontopodis, E, Hatzidaki, D, Mavroudis, D, Georgoulias, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18-08-2009; Nature Publishing Group
• Subjects: Adult; Aged; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bone Marrow - pathology; Bone Marrow Neoplasms - metabolism; Bone Marrow Neoplasms - secondary; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Cancer therapies; Chemotherapy; Clinical Study; Combined Modality Therapy; Cytokeratin; Drug Resistance; Epidemiology; Female; Gynecology. Andrology. Obstetrics; Hospitals; Humans; Kaplan-Meier Estimate; Keratin-19 - analysis; Keratin-19 - metabolism; Lymphatic system; Mammary gland diseases; Mammography; Mastectomy; Medical research; Medical sciences; Metastasis; Middle Aged; Molecular Medicine; Neoplastic Cells, Circulating - metabolism; Oncology; Radiotherapy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Treatment Outcome; Tumors; Greece; Crete; disseminated tumour cells; breast cancer; circulating tumour cells; micrometastasis; CK-19; Human; Breast disease; Breast cancer; Cytokeratin 19; Tumoral marker; Malignant tumor; Mammary gland diseases; Blood cell; Cancerology; Messenger RNA; Micrometastasis; Bone marrow; Diagnosis; Disseminated; Tumor cell; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605183

Background:
To compare detection rates and evaluate the clinical relevance of cytokeratin-19 (CK-19) mRNA-positive cells in the peripheral blood (circulating tumour cells, CTCs) and bone marrow (disseminated tumour cells; DTCs) of patients with early breast cancer.
Methods:
Paired samples of peripheral blood and bone marrow were obtained from 165 patients with stage I–II breast cancer before the initiation of adjuvant chemotherapy. In 84 patients, paired blood and bone marrow samples were also available after chemotherapy. The detection of CK-19 mRNA-positive CTCs and DTCs was assessed by real-time PCR.
Results:
CK-19 mRNA-positive CTCs and DTCs were detected in 55.2 and 57.6% of patients before chemotherapy, respectively. After chemotherapy, CTCs and DTCs were identified in 44 (52.4%) and 43 (51.2%) of the 84 patients, respectively. There was a 93.9% (McNemar;
P
=0.344) and 72.6% (McNemar;
P
=0.999) concordance between blood and bone marrow samples before and after chemotherapy, respectively. The detection of CK-19 mRNA-positive CTCs or DTCs before chemotherapy was associated with decreased overall survival (
P
=0.024 and
P
=0.015, respectively). In addition, their simultaneous detection was also associated with an increased incidence of disease-related death and decreased overall survival (
P
=0.016).
Conclusions:
The detection of CK-19 mRNA-positive CTCs using reverse transcription-PCR (RT–PCR) both before and after chemotherapy is correlated with the detection of CK-19 mRNA-positive DTCs in patients with early-stage breast cancer. The determination of the CTC status by RT–PCR conveys clinically relevant information that is not inferior to DTC status and, owing to the ease of sampling, warrants further evaluation as a tool for monitoring minimal residual disease.