Sensitivity of urinary mesothelin in patients with malignant mesothelioma.

INTRODUCTION: Malignant mesothelioma (MM) is an aggressive, uniformly fatal tumor usually caused by exposure to asbestos. Soluble mesothelin has been intensively investigated in the serum as a biomarker for this disease. As urine is less complex and less invasive to collect than serum and may be a more acceptable specimen for large-scale screening studies of asbestos-exposed individuals, we determined whether the sensitivity and specificity for MM could be improved by measuring soluble mesothelin in the urine. METHODS: Soluble mesothelin concentrations were determined using the MESOMARK assay in concurrent serum and urine samples from 70 patients with pleural MM, 111 patients with asbestos-related lung or pleural disease, and 45 patients with benign nonasbestos-related lung and pleural disease. Only patients with serum creatinine levels within the normal range were included in the study. Sensitivities were determined and receiver operator characteristic curves were generated to compare the diagnostic accuracy of mesothelin in the serum and urine. RESULTS: At a specificity of 95% relative to individuals with benign lung or pleural disease, serum mesothelin had a sensitivity of 66% and area under the curve of 0.882, whereas urinary mesothelin corrected for urine creatinine concentration had a sensitivity of 53% and area under the curve of 0.787. CONCLUSIONS: The sensitivity of urinary mesothelin does not warrant the use of urine as a biomarker specimen for MM diagnosis.

Exercise decreases plasma antioxidant capacity and increases urinary isoprostanes of IPF patients.

We tested whether markers of systemic oxidant stress were detectable in 29 typical IPF patients, and whether these increased after low level exercise. We obtained resting plasma for measurement of amino terminal pro brain natriuretic peptide (NT-proBNP), and plasma and urine samples for isoprostanes and total nitrite. Total antioxidant capacity (TAC) was measured in plasma, and H(2)O(2) was measured in urine. Subjects exercised at ˜50 W on a semi recumbent bicycle until limited by dyspnea. Samples were obtained immediately after exercise for measurement of the same variables. Plasma and urine samples were also obtained at rest from 6 normal individuals over 40 years of age solely to establish comparison values for NT-proBNP, nitrite, H(2)O(2) and TAC assays. Plasma NT-proBNP was high at rest and after exercise, suggesting pulmonary arterial hypertension. IPF patients' resting NT-proBNP concentrations apparently exceeded those of normal controls. IPF plasma isoprostanes at rest exceeded the normals. IPF urine isoprostanes increased significantly after exercise (P = 0.047 by signed rank test); and, plasma TAC decreased significantly after exercise (P < 0.001 by signed rank test). Neither plasma nor urine nitrite changed significantly after exercise. H(2)O(2) concentration was quite high after exercise in some IPF subjects' urine. IPF patients demonstrate systemic oxidant stress at rest detectable as increased isoprostanes in the circulation. An increase in urine isoprostanes and a decrease in plasma TAC after exercise suggest that reactive oxygen species (ROS) are produced during low level exercise done by IPF patients.