Sensitivity of urinary mesothelin in patients with malignant mesothelioma

Our plain-English summary of Sensitivity of urinary mesothelin in patients with malignant mesothelioma, by J. Creaney, A.W. Musk, B.W. Robinson (Journal of Thoracic Oncology, 2010).

The study

• Authors: J. Creaney, A.W. Musk, B.W. Robinson
• Journal: Journal of Thoracic Oncology
• Published: 2010;5(9):1461-6
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This diagnostic study from Perth, Western Australia, tested whether measuring the protein mesothelin in urine could detect malignant mesothelioma better than measuring it in blood serum. The authors measured soluble mesothelin with the MESOMARK assay in serum and urine samples taken at the same visit. The patients were 70 with pleural mesothelioma, 111 with benign asbestos-related disease (asbestosis or pleural plaques), 45 with other benign lung or pleural disease, and 20 with lung cancer. All had serum creatinine, a kidney blood test, in the normal range. Urinary mesothelin was undetectable in about 37% of mesothelioma patients and 82% of the other patients. Uncorrected urine levels could not tell mesothelioma from benign disease. At 95% specificity, serum mesothelin had a sensitivity of 67%. Urine mesothelin corrected for urine creatinine had a sensitivity of 60%, but this was measured only in the 44 mesothelioma and 22 benign patients with detectable urine mesothelin. The article's abstract gives different figures: 66% for serum and 53% for urine. The authors concluded that their results do not support urine-based screening of asbestos-exposed communities. They said the value of serum screening remains an open question.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic biomarker study comparing soluble mesothelin measured in matched serum and urine samples, using receiver operating characteristic (ROC) curves
• Who was studied: Patients at respiratory clinics of Sir Charles Gairdner Hospital or the Hollywood Specialist Centre in Perth, Western Australia. The groups were 70 patients with pleural malignant mesothelioma and 111 with benign asbestos-related disease (39 with asbestosis with or without pleural plaques, 72 with pleural plaques only). There were also 19 with idiopathic pulmonary fibrosis, 19 with sarcoidosis, 7 with nonmalignant exudative effusions, and 20 with lung cancer. Only patients with normal serum creatinine were included. Study dates were not given.
• Exposure: The study measured soluble mesothelin in serum and urine (MESOMARK assay) as a test for mesothelioma. Asbestos exposure was a basis for the control groups (benign asbestos-related disease), but the article does not describe fiber types, products, jobs or doses.
• Main results:
  • Serum mesothelin distinguished mesothelioma patients from patients with benign asbestos-related disease with an area under the curve (AUC) of 0.882 (95% CI, 0.826–0.925).
  • At a specificity of 95%, serum mesothelin had a sensitivity of 67% for mesothelioma, at a cutoff of 1.62 nM.
  • Using a serum cutoff of 2.5 nM, 47% of mesothelioma patients were mesothelin positive. All other participants were below 2.5 nM except two lung cancer patients.
  • Urinary mesothelin was below the assay's limit of detection in approximately 37% of mesothelioma patients (26 of 70) and 82% of non-mesothelioma patients.
  • Uncorrected urinary mesothelin (all 70 mesothelioma and 156 benign patients) had an AUC of 0.548, which the authors said showed no discriminatory value.
  • In the subset with measurable urine mesothelin (44 mesothelioma, 22 benign), urinary mesothelin corrected for urine creatinine had an AUC of 0.870 (95% CI, 0.764–0.940). This was not significantly different from serum. At 95% specificity its sensitivity was 60%.
  • The article's abstract reports different figures from the results section: serum sensitivity 66% and corrected urinary sensitivity 53% with AUC 0.787, at 95% specificity relative to benign disease.
  • In mesothelioma patients, serum and urinary mesothelin levels were significantly correlated. No correlation was seen in patients with benign conditions.
• The authors' conclusion: The authors concluded that urinary mesothelin's sensitivity does not justify using urine for mesothelioma diagnosis, and that their results do not support urine-based screening of asbestos-exposed communities. They added that the value of screening with serum mesothelin remains an open question.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Malignant Mesothelioma, Biomarker, MESOMARK® Assay.

Related studies

• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma — J. Creaney, I. van Bruggen, et al. (2007)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)
• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma — J. Creaney, N.J. Olsen, et al. (2010)
• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2010)

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