RESUMO
BACKGROUND: The assessment of circulating tumor cells (CTCs) has been shown to enable monitoring of treatment response and early detection of metastatic breast cancer (MBC) recurrence. The aim of this study was to compare a well-established CTC detection method based on immunomagnetic isolation with a new, filtration-based platform. METHODS: In this prospective study, two 7.5 ml blood draws were obtained from 60 MBC patients and CTC enumeration was assessed using both the CellSearch® and the newly developed filtration-based platform. We analyzed the correlation of CTC-positivity between both methods and their ability to predict prognosis. Overall survival (OS) was calculated and Kaplan-Meier curves were estimated with thresholds of ≥1 and ≥5 detected CTCs. RESULTS: The CTC positivity rate of the CellSearch® system was 56.7% and of the filtration-based platform 66.7%. There was a high correlation of CTC enumeration obtained with both methods. The OS for patients without detected CTCs, regardless of the method used, was significantly higher compared to patients with one or more CTCs (p < 0.001). The median OS of patients with no CTCs vs. ≥ 1 CTC assessed by CellSearch® was 1.83 years (95% CI: 1.63-2.02) vs. 0.74 years (95% CI: 0.51-1.52). If CTCs were detected by the filtration-based method the median OS times were 1.88 years (95% CI: 1.74-2.03) vs. 0.59 years (95% CI: 0.38-0.80). CONCLUSIONS: The newly established EpCAM independently filtration-based system is a suitable method to determine CTC counts for MBC patients. Our study confirms CTCs as being strong predictors of prognosis in our population of MBC patients.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Filtração/métodos , Citometria de Fluxo , Células Neoplásicas Circulantes/patologia , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Imunofluorescência , Humanos , Separação Imunomagnética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
MicroRNAs are auspicious candidates for a new generation of biomarkers. The detection of microRNA panels in body fluids promises early diagnosis of many diseases, including cancer or acute coronary syndrome. For a fast, sensitive, and specific detection of microRNA panels on the bedside, medical point-of-care systems that measure those biomarkers are required. As microchips are promising technical tools for a robust signal measurement at biochemical interfaces, we developed an assay for the electrochemical multiplex quantification of microRNAs on a CMOS chip with interdigitated gold electrode sensor positions. The method is based on the formation of a tripartite hybridization complex and subsequent both-sided ligation of the target nucleic acid to a reporter and capture strand. With a time to results of 30 min, the reported assay achieves a limit of detection below 1 pM, at a specificity down to single mismatch discrimination. It also offers very good signal dynamics between 1 pM and 1 nM, thus, allowing reliable quantification of the detected microRNAs and easy implementation into automated devices due to a simple workflow.