Biomarkers for mesothelioma

Our plain-English summary of Biomarkers for mesothelioma, by A. Scherpereel, Y.C. Lee (Current Opinion in Pulmonary Medicine, 2007).

The study

• Authors: A. Scherpereel, Y.C. Lee
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2007;13(4):339-443
• Type of article: Review
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Mesothelioma is an incurable cancer and its global incidence continues to increase. There has been strong interest in the search for a biomarker that would be of value for the diagnosis, prognosis and disease monitoring of mesothelioma. Large series evaluating the use of novel candidate markers have recently been published.

Recent Findings: To date, global gene profiling studies have failed to find a molecule that reliably captures all subtypes of mesothelioma, and differentiates it from benign pathologies and metastatic carcinomas. Soluble mesothelin-related peptide (SMRP), osteopontin and megakaryocyte potentiating factor have been assessed as markers. SMRP testing is clinically available and provides reasonable diagnostic sensitivity and specificity when applied to serum or pleural fluid. Elevated SMRP levels can occur in metastatic, especially ovarian and pancreatic, adenocarcinomas. False negatives are common with sarcomatoid mesothelioma. SMRP levels may reflect tumor load and disease progression. The role of SMRP in predicting mesothelioma development in subjects exposed to asbestos has raised interest. Osteopontin lacks specificity as a diagnostic marker for mesothelioma but may have value in disease monitoring.

Summary: The proposed markers have insufficient accuracy to replace cytohistology as the gold standard for diagnosis for mesothelioma. Elevated SMRP levels raise suspicion of mesothelioma although negative values do not exclude disease. Its role in disease monitoring in patients and in predicting disease development in at-risk individuals warrant further study.

In plain English

This article was a review: the authors summarized published research on blood and body-fluid tests (biomarkers) for mesothelioma. They reported that, despite gene-profiling studies, no molecule had been found that met the criteria of an ideal diagnostic biomarker. For soluble mesothelin-related peptide (SMRP), one cited study of 44 mesothelioma patients and 160 others reported serum sensitivity of 84% and specificity of virtually 100%. Pleural fluid studies reported sensitivity and specificity of 77% and 76% (France) and 67% and 98% (Western Australia, 234 patients). Cited work found SMRP raised in epithelioid but not sarcomatoid mesothelioma. In one cited study of stored serum from 40 asbestos-exposed people, seven had elevated SMRP, and three of those developed mesothelioma within 5 years. None of the 33 with normal levels developed mesothelioma after 8 years. The authors judged osteopontin unattractive for diagnosis because of low specificity. They noted that published cut-offs were chosen after the fact and had not been tested in separate groups. The authors concluded that SMRP cannot replace tissue diagnosis as the gold standard.

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 of published studies (narrative review)
• Who was studied: No new patients were studied. The authors reviewed published research on gene profiling and on three candidate markers (SMRP, osteopontin and megakaryocyte potentiating factor) in people with mesothelioma, people with other diseases, and people exposed to asbestos.
• Exposure: This was not an exposure study. Asbestos exposure appears only as the background of the at-risk groups in the reviewed screening studies. No fiber types are named.
• Main results:
  • Across the reviewed gene-profiling and other work, no molecule had been found that fulfilled the criteria of an ideal diagnostic biomarker for mesothelioma.
  • Robinson et al. (cited) measured serum SMRP in 44 patients with mesothelioma and 160 others with various benign or malignant pleural or pulmonary diseases. They reported sensitivity of 84% and specificity of virtually 100%.
  • A cited study found elevated SMRP levels only in epithelioid mesotheliomas, not in sarcomatoid mesotheliomas.
  • In pleural fluid, SMRP sensitivity and specificity were 77% and 76% in a multicenter study from France.
  • In pleural fluid, SMRP sensitivity and specificity were 67% and 98% in a Western Australian cohort of 234 patients.
  • Robinson et al. (cited) tested stored serum from 40 asbestos-exposed subjects. Seven had elevated SMRP, and three of those developed mesothelioma (and one developed lung cancer) within 5 years.
  • In the same cited study, none of the 33 asbestos-exposed subjects with normal serum SMRP developed mesothelioma after 8 years of follow-up.
  • In cited studies, SMRP levels did not predict prognosis in mesothelioma after adjusting for histologic subtypes.
  • Pass et al. (cited) reported a diagnostic sensitivity of 77% and specificity of 85% for serum osteopontin in mesothelioma.
  • The authors judged that the low specificity of osteopontin makes it unattractive as a diagnostic biomarker.
  • A cited study found serum megakaryocyte potentiating factor elevated in 91% of 56 patients with mesothelioma compared with healthy controls.
• The authors' conclusion: The authors concluded that, of the reported candidates, SMRP in serum or pleural fluid appears the most useful. Because other tumors can raise SMRP and it misses sarcomatoid (and some biphasic) mesotheliomas, they concluded it cannot replace histopathologic diagnosis as the gold standard.
• Limitations the authors state:
  • In the published SMRP studies, sensitivity and specificity were calculated using cut-offs chosen after the fact. Whether the same cut-offs work in separate groups had not been tested.
  • The screening finding in asbestos-exposed subjects comes from a small group. The authors stated that larger prospective studies are needed to confirm it.
  • The authors noted there is no evidence that detecting mesothelioma early changes the outcome.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Prognosis, Carcinoma, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Osteopontin, Adenocarcinoma.

Related studies

• Serum and pleural fluid biomarkers for mesothelioma — J. Creaney, B.W. Robinson (2009)
• 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)
• Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study — K. Hollevoet, J. Van Cleemput, et al. (2011)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)
• A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma — B.T.V. Duong, L. Wu, et al. (2020)
• A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma — I. Raiko, H.P. Rihs, et al. (2017)

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