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

Xenidis, N.; Perraki, Maria; Kafousi, Maria; Apostolaki, Stella; Bolonaki, I.; Stathopoulou, Aliki; Kalbakis, Kostas; Androulakis, N.; Kouroussis, Charalambos; Pallis, Athanasios A.; Christophylakis, Charalambos; Argyraki, Katerina; Lianidou, Evi; Stathopoulos, Stathis; Georgoulias, Vassilis; Mavroudis, Dimitris

doi:10.1200/jco.2005.04.5948

Cited by 258 publications

(168 citation statements)

References 24 publications

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“…Several studies have shown that the detection of bone marrow (DTCs) [2][3][4] or peripheral blood [CTCs; [5][6] tumor cells is associated with an increased risk of relapse and reduced survival in patients with stage I/III breast cancer. In most of the studies, the detection of CTCs was performed using CK19 as a marker of epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The detection of occult tumor cells either in the bone marrow or the peripheral blood has been demonstrated to represent an independent prognostic factor for disease relapse and reduced survival [2][3][4][5][6]. Indeed, a meta-analysis involving 4,703 patients with stage I-III breast cancer confirmed the independent prognostic value of DTCs [7].…”

Section: Introductionmentioning

confidence: 98%

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Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Apostolaki

Perraki

Kallergi

et al. 2008

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Apostolaki

Perraki

Kallergi

et al. 2008

Breast Cancer Res Treat

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“…More recent reports have demonstrated the prognostic significance of CK19 mRNA-positive CTCs in patients with early stage breast cancer [103][104][105]. Studies that investigated the prognostic value of CTCs/DTCs at the time of completion of adjuvant therapy [42, 106,107] showed that the detection of DTCs [42,108] and CTCs [106] after the completion of chemotherapy is associated with an unfavorable clinical outcome [103,105]; further reviewed by Ignatiadis et al [109].…”

Section: Cytokeratin 19mentioning

confidence: 99%

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

Friel

Corcoran

Crown

et al. 2010

Breast Cancer Res Treat

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Early detection of cancer is vital to improved overall survival rates. At present, evidence is accumulating for the clinical value of detecting occult tumor cells in peripheral blood, plasma, and serum specimens from cancer patients. Both molecular and cellular approaches, which differ in sensitivity and specificity, have been used for such means. Circulating tumor cells and extracellular nucleic acids have been detected within blood, plasma, and sera of cancer patients. As the presence of malignant tumors are clinically determined and/or confirmed upon biopsy procurement-which in itself may have detrimental effects in terms of stimulating cancer progression/metastases-minimally invasive methods would be highly advantageous to the diagnosis and prognosis of breast cancer and the subsequent tailoring of targeted treatments for individuals, if reliable panels of biomarkers suitable for such an approach exist. Herein, we review the current advances made in the detection of such circulating tumor cells and nucleic acids, with particular emphasis on extracellular nucleic acids, specifically extracellular mRNAs and discuss their clinical relevance.

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“…We have reported earlier that the detection of CTCs before the initiation of adjuvant chemotherapy in patients with operable breast cancer, irrespective of the presence of axillary lymph node involvement (Stathopoulou et al, 2002;Wiedswang et al, 2003;Xenidis et al, 2006), or an oestrogen/progesterone or HER2 receptor expression (Ignatiadis et al, 2007), is also an independent factor associated with decreased DFS and OS.…”

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confidence: 94%

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

et al. 2009

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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 ¼ 0.344) and 72.6% (McNemar; P ¼ 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 ¼ 0.024 and P ¼ 0.015, respectively). In addition, their simultaneous detection was also associated with an increased incidence of disease-related death and decreased overall survival (P ¼ 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.

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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

Abstract: 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.

Cited by 258 publications

References 24 publications

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

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

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