Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma

Our plain-English summary of Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma, by I. Pantazopoulos, P. Boura, T. Xanthos, et al (The European Respiratory Journal, 2013).

The study

• Authors: I. Pantazopoulos, P. Boura, T. Xanthos, K. Syrigos
• Journal: The European Respiratory Journal
• Published: 2013;41(3):706-15
• Type of article: Review
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice. Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the "optimal" diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.

In plain English

This was a non-systematic review, not a new study. The authors searched PubMed up to 15 March 2012 and included 71 English-language articles on three proposed mesothelioma markers: mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin. Mesothelin and MPF were described as having good specificity but sub-optimal sensitivity. Serum mesothelin was raised in the epithelioid but not the sarcomatoid subtype, yet was negative in almost half of epithelioid cases, especially at early stages. There was no agreed cut-off value, and kidney function affected levels. In one reviewed screening study, 15 of 538 asbestos-exposed workers followed for 12 months had mesothelin above 2.5 nmol per litre. Of those, one had chronic renal failure but no malignancy, one early-stage lung adenocarcinoma, one a suspected cardiac tumour; the other 12 had no malignancy noted. Osteopontin was described as a marker of the duration of asbestos exposure that lacked specificity for mesothelioma. The authors concluded that, in the near future, the markers would most probably serve to monitor response to therapy rather than guide diagnosis or risk assessment in asbestos-exposed populations.

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: Non-systematic literature review
• Who was studied: 71 English-language published articles found through PubMed (no lower date limit; last search 15 March 2012), plus reference lists and related-article searches. The reviewed studies involved patients with malignant mesothelioma, asbestos-exposed people and various control groups.
• Exposure: Not an exposure study. The review covered three candidate markers measured in serum, plasma, pleural fluid or urine: mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin. No specific asbestos fiber types were analysed. A planned study in Cappadocia, Turkey, concerning environmental erionite exposure was mentioned.
• Main results:
  • Across the studies reviewed, mesothelin and MPF had good specificity but sub-optimal sensitivity for detecting malignant mesothelioma.
  • Reviewed studies found raised serum mesothelin in patients with the epithelial (epithelioid) subtype but not in patients with the sarcomatoid subtype.
  • Mesothelin and MPF were negative in the sarcomatoid subtype and in almost half of epithelioid mesothelioma, especially in the early stages. The review also states that elevated serum mesothelin is present in only 50 to 75% of patients with epithelioid mesothelioma.
  • No cut-off value for mesothelin had been established; various cut-offs were proposed in different studies.
  • In the screening study by Park et al., 15 of 538 occupationally asbestos-exposed individuals followed for 12 months had soluble mesothelin above 2.5 nmol per litre. Of those 15, one had chronic renal failure with no malignancy, one had early-stage lung adenocarcinoma and one had a suspected cardiac tumour. No malignancy was noted in the remaining 12.
  • In one reviewed study, pleural fluid mesothelin had higher sensitivity than cytological examination but lower specificity (sensitivity 71% versus 35%; specificity 89% versus 100%).
  • Mesothelin levels were reported to fall after tumour resection and rise with progression.
  • Reduced kidney function was reported to falsely increase mesothelin concentrations.
  • In a study by Pass et al., osteopontin distinguished asbestos-exposed patients from stage I mesothelioma patients with a sensitivity of 84.6% and a specificity of 88.4% at a cut-off value of 62.4 ng per mL.
  • Osteopontin was described as a marker of the duration of asbestos exposure that lacks specificity for mesothelioma.
• The authors' conclusion: The authors concluded that extensive validation and further research are required. They judged that in the near future these markers are most probably useful for monitoring response to therapy, rather than for guiding diagnostic decisions or assessing risk in asbestos-exposed populations.
• Limitations the authors state:
  • The authors noted that none of the three markers had been rigorously validated in a blinded fashion using prospectively collected specimens from trials in which mesothelioma developed.
  • The authors noted that small study populations limited the statistical power of the prognostic studies reviewed.

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, Osteopontin, Mesothelioma, Prognosis, Biomarker, Sarcomatoid, Epithelioid, Asbestos Exposure.

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)
• Mesothelin and osteopontin — I. Pantazopoulos, T. Xanthos, et al. (2013)
• Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers — M.K. Felten, K. Khatab, et al. (2014)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)

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