Low specificity of cytokeratin 19 reverse transcriptase-polymerase chain reaction analyses for detection of hematogenous lung cancer dissemination.

1995 ◽  
Vol 13 (11) ◽  
pp. 2769-2775 ◽  
Author(s):  
M Krismann ◽  
B Todt ◽  
J Schröder ◽  
D Gareis ◽  
K M Müller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Lung Tumor ◽  
Cytokeratin 19 ◽  
Healthy Controls ◽  
Rt Pcr ◽  
Lung Cancer Patients ◽  
Tumor Dissemination ◽  
Breast And Prostate Cancer

PURPOSE Sensitive detection of systemic tumor dissemination in lung cancer patients is important for selection of appropriate treatment modalities. Based on recent promising data that showed reverse transcriptase-polymerase chain reaction (RT-PCR) analyses for cytokeratin 19 (CK-19) expression in peripheral-blood or bone marrow samples to be a rapid and highly sensitive method for detection of hematogenous tumor dissemination in patients with breast and prostate cancer, we evaluated the specificity of this assay system in lung cancer patients and a large number of healthy controls. PATIENTS AND METHODS We examined CK-19 mRNA expression by RT-PCR in 17 lung cancer cell lines and in peripheral-blood samples of 50 lung tumor patients and 65 healthy controls. RESULTS Expression of CK-19 mRNA was observed in all lung cancer cell lines and in 50% of peripheral-blood samples from lung tumor patients. However, under the experimental conditions analyzed, at least 20% of the control samples were positive for CK-19 mRNA expression. CONCLUSION Contrary to prior reports, RT-PCR may detect non-tissue-specific constitutive low-level (illegitimate) expression of CK-19 mRNA in peripheral-blood mononuclear (PBMN) cells in a significant number of healthy controls. This finding may not only hamper the use of this assay system in lung cancer patients, but also questions its proposed applicability in patients with other epithelial tumors such as breast and prostate cancer.

scholarly journals High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2966
Author(s):  
Dagmar Riemann ◽  
Wolfgang Schütte ◽  
Steffi Turzer ◽  
Barbara Seliger ◽  
Miriam Möller
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Risk Factor ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Therapy Response ◽  
Inhibitor Therapy ◽  
Strong Positive Correlation ◽  
Blood Monocytes ◽  
Lung Cancer Patients

The aim of this study was to investigate the expression of the coinhibitory molecule PD-L1/CD274 in monocytes and dendritic cells (DC) in the blood of lung cancer patients undergoing PD1 inhibitor therapy and to correlate data with patient’s outcome. PD-L1/CD274 expression of monocytes, CD1c+ myeloid DC (mDC) and CD303+ plasmacytoid DC (pDC) was determined by flow cytometry in peripheral blood at immunotherapy onset. The predictive value of the PD-L1/CD274-expression data was determined by patients’ survival analysis. Patients with a high PD-L1/CD274 expression of monocytes and blood DC subpopulations rarely responded to PD1 inhibitor therapy. Low PD-L1/CD274 expression of monocytes and DC correlated with prolonged progression-free survival (PFS) as well as overall survival (OS). The highest PD-L1/CD274 expression was found in CD14+HLA-DR++CD16+ intermediate monocytes. Whereas the PD-L1/CD274 expression of monocytes and DC showed a strong positive correlation, only the PD-L1/CD274 expression of DC inversely correlated with DC amounts and lymphocyte counts in peripheral blood. Our results implicate that a high PD-L1/CD274 expression of blood monocytes and DC subtypes is a risk factor for therapy response and for the survival of lung cancer patients undergoing PD1 inhibitor therapy.

scholarly journals Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ryo Arai ◽  
Sayo Soda ◽  
Tomoko Okutomi ◽  
Hiroko Morita ◽  
Fumito Ohmi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Lipid Accumulation ◽  
Stage Iii ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Treatment Naïve ◽  
Anticancer Immunity

We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs) and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed.

scholarly journals High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients

2017 ◽  
Vol 114 (10) ◽  
pp. 2544-2549 ◽  
Author(s):  
Yin Tang ◽  
Zhuo Wang ◽  
Ziming Li ◽  
Jungwoo Kim ◽  
Yuliang Deng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Pleural Fluid ◽  
High Throughput ◽  
Targeted Therapies ◽  
Peripheral Blood ◽  
Detection Scheme ◽  
Lung Cancer Patients

Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid. We describe a highly sensitive approach for rapid detection of metabolically active tumor cells in MPE via exploiting the altered glucose metabolism of tumor cells relative to benign cells. Metabolically active tumor cells with high glucose uptake, as evaluated by a fluorescent glucose analog (2-NBDG), are identified by high-throughput fluorescence screening within a chip containing 200,000 addressable microwells and collected for malignancy confirmation via single-cell sequencing. We demonstrate the utility of this approach through analyzing MPE from a cohort of lung cancer patients. Most candidate tumor cells identified are confirmed to harbor the same driver oncogenes as their primary lesions. In some patients, emergence of secondary mutations that mediate acquired resistance to ongoing targeted therapies is also detected before resistance is manifested in the clinical imaging. The detection scheme can be extended to analyze peripheral blood samples. Our approach may serve as a valuable complement to cytology in MPE diagnosis, helping identify the driver oncogenes and resistance-leading mutations for targeted therapies.

Detection of Cytokeratin-19 in Peripheral Blood of Breast Cancer Patients: Results from a Systematic Review/Meta-Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5314-5314
Author(s):  
Heloisa P. Soares ◽  
Rodrigo Santucci ◽  
Ambuj Kumar ◽  
Benjamin Djulbegovic ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Meta Analysis ◽  
Cytokeratin 19 ◽  
Breast Cancer Patients ◽  
Rt Pcr ◽  
Diagnostic Specificity

Abstract Background: The identification of occult micrometastatic disease is potentially important in management of breast cancer (BC) patients. Therefore, detection of cytokeratin 19 (CK-19) and others molecular markers using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques to detect micrometastases could have significant implications in prevention, early detection and treatment of breast cancer. Objective: To assess the diagnostic specificity and sensitivity of detection of CK-19 in the peripheral blood (PB) of BC patients as well as to assess its relation to prognostic factors and implication on survival. Methods: We conducted a systematic review/meta-analysis of all studies that analyzed CK-19 in the PB of BC patients. We searched MEDLINE, LILACS and Cochrane Database of Systematic Reviews (last search June 2004). Studies that had at least 10 BC patients and controls and evaluated the presence of CK-19 in PB using RT-PCR were included in this review. Diagnostic sensitivity was defined as the percentage of detection of CK-19 in patients with histological proven diagnosis of breast cancer. The specificity was defined as the percentage of negative tests for CK-19 in the control group (healthy individuals or non breast cancer patients). Results: Out of 1842 relevant studies that were identified, 26 met our inclusion criteria, enrolling 2398 patients (1176 treatment and 1222 controls). Results showed that PCR had an overall diagnostic sensitivity of 0.39 (95% CI: 0.36–0.42) and diagnostic specificity of 0.83 (95% CI: 0.76–0.87) regardless of the breast cancer stage. Six studies researched the association between CK-19 and well established prognostic factors (i.e. positive axillary lymph nodes, hormonal receptors, tumor size); however data were not available for quantitative synthesis. Survival was poorly reported making impossible to generate any conclusion about the implication of detection of CK-19 on prognosis. When studies were critically appraised, we also identified many methodological weaknesses in the design, conduct and the analysis of these studies (e.g. use of multiple control arms, use of non-consecutive patients, different timing of sample collection, inclusion of all stages of breast cancer and differential work-up in the study & control groups) hence resulting in biased findings due to selection, verification, detection and spectrum bias. Conclusion: The existing body of evidence regarding the assessment and prognostic value of CK-19 using RT-PCR techniques is poor and needs ample improvement before the initiation of its clinical application.

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