Serum and pleural fluid biomarkers for mesothelioma

Our plain-English summary of Serum and pleural fluid biomarkers for mesothelioma, by J. Creaney, B.W. Robinson (Current Opinion in Pulmonary Medicine, 2009).

The study

• Authors: J. Creaney, B.W. Robinson
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2009;15(4):366-70
• Type of article: Review
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Malignant mesothelioma is an asbestos-induced, aggressive tumour. In centres across the world, research has focused on evaluating biomarkers for malignant mesothelioma screening, diagnosis, prognostication and monitoring. With the incidence of malignant mesothelioma expected to increase, it is timely to review the current status of biomarkers in this field.

Recent Findings: The majority of recent studies have evaluated the commercial MESOMARK assay in a diagnostic setting. Studies have clarified that soluble-shed mesothelin as well as mesothelin-related peptide are targets of the assay. The assay sensitivity ranges from 50% at diagnosis to 84% in advanced disease. The assay has a high level of specificity relative to benign lung and pleural conditions and is positive in 10-15% of other malignancies. In a prospective screen of 538 asbestos-exposed workers, 2.8% were positive; one had lung cancer that was subsequently successfully treated. The biomarkers megakaryocyte potentiating factor, osteopontin and CA125, either alone or in combination with soluble mesothelin, have also been assessed.

Summary: To date, soluble mesothelin remains the best available biomarker for malignant mesothelioma. However, a lack of sensitivity for early-stage disease and for all malignant mesothelioma histologies provides motivation for the search of novel malignant mesothelioma biomarkers with greater sensitivity, especially for very early disease.

In plain English

This article was a review by the authors, from the National Centre for Asbestos Related Diseases in Western Australia, of blood (serum) and pleural fluid tests, called biomarkers, for malignant mesothelioma. It mainly covered soluble mesothelin, measured by a commercial test called MESOMARK. It also covered megakaryocyte potentiating factor (MPF), osteopontin and CA125. In the studies reviewed, soluble mesothelin was higher in mesothelioma patients than in patients with other lung and pleural diseases, but it was also raised in some other cancers. The authors estimated that 11% of about 170 lung cancer patients were above the test cut-off. In one reviewed study of 66 mesothelioma patients, at 95% specificity, sensitivity was 34% for MPF, 47% for osteopontin and 73% for soluble mesothelin. Combining markers did not do better than mesothelin alone. In a reviewed screening study of 538 occupationally asbestos-exposed people, 15 had raised mesothelin, and one of them had early lung adenocarcinoma. That cohort had only been followed for 12 months. The authors concluded that no ideal biomarker had been found and that no current biomarker would be sufficient for screening in a one-step protocol.

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: Review (summary and update of published studies on mesothelioma biomarkers); no new data were collected
• Who was studied: Published studies, from centres across the world, of malignant mesothelioma patients, control groups (healthy people, asbestos-exposed people, patients with benign disease or other cancers) and asbestos-exposed workers being screened
• Exposure: Asbestos exposure, mostly occupational, as the background cause of mesothelioma. The review itself was about blood and fluid biomarkers (soluble mesothelin, MPF, osteopontin, CA125 and others), not about fiber types.
• Main results:
  • In the authors' earlier study with the Hellström group, 37 of 44 malignant mesothelioma patients (84%) had elevated soluble mesothelin-related protein in serum, compared with healthy asbestos-exposed and non-exposed controls
  • Across reviewed studies, the soluble mesothelin assay had an estimated specificity of 95% or more relative to patients with benign asbestos-related diseases, including diffuse pleural thickening and asbestosis
  • Soluble mesothelin was also raised in other cancers. One reviewed series found it elevated in less than 10% of 500 patients with other cancers. The authors estimated that 11% of about 170 lung cancer patients were above a 2.5 nmol/l cut-off, and about 12 of 139 newly diagnosed lung cancer patients in another series.
  • Mesothelin measured in pleural fluid appeared better than serum mesothelin at telling mesothelioma apart from other cancers
  • In a reviewed study of 66 mesothelioma patients, at 95% specificity, sensitivity for malignant mesothelioma was 34% for MPF, 47% for osteopontin and 73% for soluble mesothelin
  • In three reviewed studies, combining markers did not improve sensitivity over soluble mesothelin alone
  • In a reviewed prospective study (Park et al.) of 538 occupationally asbestos-exposed individuals, 15 (3%) had soluble mesothelin above 2.5 nmol/l. Of these, one had chronic renal failure with no malignancy, one had early stage lung adenocarcinoma, one had a suspected cardiac tumour, and 12 had no malignancy noted.
  • In a reviewed retrospective study (Roe et al.) of serum taken before diagnosis from 47 mesothelioma cases, there was no significant association between mesothelin level and mesothelioma risk. The samples had been taken a median of 13 years before diagnosis.
• The authors' conclusion: The authors concluded that soluble mesothelin remained the best available biomarker but that no ideal biomarker for pleural malignant mesothelioma had been identified. They also concluded that screening for asbestos-related malignancy was still a worthy aim, but that no currently available biomarker would be sufficient for it in a one-step protocol.
• Limitations the authors state:
  • The authors noted that the lack of a standard treatment for mesothelioma made it difficult to compare data on mesothelin and prognosis
  • The authors noted that the screening cohort study had only 12 months of follow-up
  • The authors estimated MPF levels from graphs in a published study and could not tell whether the difference was statistically significant
  • The authors noted that screening would produce false negative as well as false positive results

Topics

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

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

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)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos — M. Bayram, I. Dongel, et al. (2014)
• Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study — K. Hollevoet, J. Van Cleemput, et al. (2011)
• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma — J. Creaney, N.J. Olsen, et al. (2010)

Browse more research in Current Opinion in Pulmonary Medicine, or return to medical research.