Transcription expression and clinical significance of VEGF mRNA and endostatin mRNA in pleural effusions of patients with lung cancer
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.Diagnostic Cytopathology (Impact Factor: 1.12). 04/2012; 40(4):287-91. DOI: 10.1002/dc.21546
The aim of this study was to evaluate the individual and combined diagnostic utility of vascular endothelial growth factor (VEGF) mRNA and endostatin mRNA in pleural effusions of patients with lung cancer. Transcription levels of VEGF and endostatin were detected by reverse transcription polymerase chain reaction (RT-PCR) in pleural effusions of patients with lung cancer (92 cases) and with lung benign disease (36 cases). Both VEGF mRNA and endostatin mRNA was significantly higher in malignant, AC, and SCC effusions than in benign effusions (P < 0.01). In the subgrouping, VEGF mRNA was obviously higher than endostatin mRNA in malignant and AC effusions (P < 0.01), whereas VEGF mRNA and endostatin mRNA did not differ between AC group and SCC group (P > 0.05). In single, VEGF mRNA had the highest sensitivity (82.6%) and accuracy (84.3%), whereas endostatin mRNA had the highest specificity (100%). When combinations of VEGF mRNA and endostatin mRNA were evaluated together, they gave a high-diagnostic performance: sensitivity of 95.7% and accuracy of 93.8%, respectively. The detection of VEGF mRNA and endostatin mRNA appears to be suitable for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions, they could be useful to diagnose the pleural micrometastasis.
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ABSTRACT: Since the diagnostic accuracy of conventional examinations for malignant pleural effusion (MPE) is limited, a number of studies have investigated the utility of pleural vascular endothelial growth factor (VEGF) in the diagnosis of MPE. The present meta-analysis aimed to determine the overall accuracy of a VEGF test in the diagnosis of MPE. A systematic review of studies published in English was conducted and the data concerning the accuracy of pleural VEGF assays in the diagnosis of MPE were pooled with random effects models. The overall test performance was summarized using receiver operating characteristic curves. Ten studies, based on 1,025 patients, met the inclusion criteria for the meta-analysis and the summary estimates for VEGF in the diagnosis of MPE were: sensitivity 0.75 [95% confidence interval (CI), 0.72-0.79], specificity 0.72 (95% CI, 0.68-0.76), positive likelihood ratio 2.94 (95% CI, 1.97-4.41), negative likelihood ratio 0.38 (95% CI, 0.27-0.51) and diagnostic odds ratio 9.05 (95% CI, 4.60-17.80). The summary receiver operating characteristic curve indicated that the maximum joint sensitivity and specificity was 0.75; the area under the curve was 0.82. Our findings suggest that the determination of pleural VEGF may improve the accuracy of MPE diagnosis, while the results of VEGF assays should be interpreted in parallel with conventional test results and other clinical findings.
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ABSTRACT: Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to be efficient in suppressing the accumulation of pleural fluid. However, whether intrapleural delivery of bevacizumab can be used to treat MPE remains unknown. The aim of the present study was to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. A total of 72 NSCLC study subjects with MPE were randomly assigned to one of two groups. The first group received intrapleural bevacizumab (300 mg) with cisplatin (30 mg) therapy and the second group received intrapleural cisplatin (30 mg) therapy alone. Pleural fluid was collected from both groups prior to and following treatment. The levels of VEGF and carcinoembryonic antigen (CEA) in the pleural fluid were determined by ELISA. In 70 evaluable study subjects, the curative efficacy in the bevacizumab group was significantly higher than that found in the cisplatin group (83.33 vs. 50.00%, respectively; p<0.05). Therapy with combined bevacizumab plus cisplatin significantly reduced VEGF levels in the pleural fluid (p<0.01). In the bevacizumab group, the levels of VEGF in the pleural fluid were significantly lower compared to those of the cisplatin group after treatment, which showed greater efficacy (p<0.01). In addition, combination therapy showed greater efficacy in the patients with high levels of VEGF expression (p<0.01). There was no significant difference in grade III/IV adverse events between the two groups. All procedures were well tolerated by the patients. Combined intrapleural therapy with bevacizumab and cisplatin was effective and safe in managing NSCLC-mediated MPE. We propose that VEGF expression levels in MPE could serve as a prognostic marker for bevacizumab therapy.
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ABSTRACT: Background and objectiveBronchial brushing is important for cytological diagnosis of lung carcinoma; however, cytological evaluation alone remains relatively insensitive. The aim of this study was to assess the diagnostic utility of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) and specificity protein 1 (SP1) mRNA in bronchial brushings in patients with or without lung cancer.MethodsVEGF mRNA and SP1 mRNA were measured in liquid-based cells from bronchial brushings in patients with verified lung cancer (n = 93) and with benign lung disease that included tuberculosis (n = 51). This was done using the reverse-transcription polymerase chain reaction.ResultsBoth VEGF mRNA and SP1 mRNA were significantly more likely to be expressed in the cancer group than in the control (benign) group, whatever their cell type. It was also more often found in the tuberculosis group than in the inflammation group (P < 0.01). In the cancer group, VEGF mRNA was significantly correlated with SP1 mRNA (P < 0.01). Of the 36 false negative cytology results, 30 gave positive results for VEGF mRNA and 34 for SP1 mRNA. The four false positive VEGF results were all diagnosed as tuberculosis. VEGF mRNA gave the highest diagnostic performance with serial use: sensitivity 89.2% and accuracy 90.3%. This was significantly better than cytology (P < 0.01).Conclusions Detection of VEGF mRNA and SP1 mRNA in bronchial brushing cells may be used as an ancillary tool to cytological diagnosis for detection of early-stage lung cancer. It may also help distinguish tuberculosis from other causes of lung inflammation.
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