Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma

Our plain-English summary of Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma, by J. Creaney, N.J. Olsen, F. Brims, et al (Cancer Epidemiology, Biomarkers & Prevention, 2010).

The study

• Authors: J. Creaney, N.J. Olsen, F. Brims, I.M. Dick, A.W. Musk, N.H. de Klerk, S.J. Skates, B.W. Robinson
• Journal: Cancer Epidemiology, Biomarkers & Prevention
• Published: 2010;19(9):2238-46
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma.

Methods: Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay.

Results: Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis.

Conclusion: In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group.

Impact: Future studies examining a combination of biomarkers could improve sensitivity of screening.

(c)2010 AACR.

In plain English

This Australian study tested stored blood samples for mesothelin, a blood protein, to see whether it rose before diagnosis of malignant mesothelioma. The people who developed mesothelioma and one comparison group came from a cancer prevention program for people exposed to blue asbestos (crocidolite) through work or residence at Wittenoom. The authors tested samples from 106 people who later developed mesothelioma, 99 exposed program members who stayed cancer-free for 10 years, and 109 unexposed people from a Busselton health survey. In healthy exposed people, levels were stable over 4 years and did not correlate with estimated exposure. Using a cutoff of 2.5 nmol/L, 17 of the 106 people who developed mesothelioma had a raised level in their second-last sample before diagnosis. That sample was taken a median of 8 months before diagnosis. When that sample was compared with each person's own earlier samples, 33 of 82 analyzable people showed a rise. The authors concluded that mesothelin was elevated in between 15% and 40% of this group before diagnosis. They said many factors need addressing before large-scale testing is encouraged.

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: Case-control study using stored serum samples: a retrospective study of samples collected prospectively within a cohort
• Who was studied: 106 people with confirmed mesothelioma (99 male, 7 female) diagnosed 1994 to 2006 who had blood samples stored before diagnosis, from the Wittenoom cancer prevention program in Western Australia. The 99 asbestos-exposed controls, who had 10 years of follow-up free of malignancy, came from the same program. The 109 non-asbestos-exposed healthy controls came separately from the Busselton Population Medical Research Foundation (Busselton Health Survey).
• Exposure: Blue asbestos (crocidolite), through work for the Australian Blue Asbestos Company or residence in Wittenoom Township. Cumulative exposure was estimated in fiber-years per mL. Among the 77 exposed controls with estimates it ranged from 0.1 to 253 fiber-years/mL.
• Main results:
  • In people who stayed malignancy-free, mesothelin levels were not significantly different between the non-asbestos-exposed group (median 0.701 nmol/L, interquartile range 0.383 to 1.117) and the asbestos-exposed group (median 0.638, interquartile range 0.386 to 0.972).
  • In the 77 asbestos-exposed controls with exposure estimates, there was no correlation between mesothelin concentration and estimated degree of asbestos exposure.
  • In asbestos-exposed controls with samples taken 4 years apart (44 individuals per the figure legend), mesothelin levels were stable: Pearson's correlation 0.96, P less than 0.0001.
  • One asbestos-exposed control had rising mesothelin over time. This person had worsening kidney function (creatinine 210 micromol/L at the end of 1990, over 600 micromol/L in September 1994) and began peritoneal dialysis.
  • Using a cutoff of 2.5 nmol/L, 17 of the 106 people who developed mesothelioma had elevated mesothelin in the second-last (penultimate) sample before diagnosis. That sample was taken a median of 8 months before diagnosis.
  • In people who developed mesothelioma, the median mesothelin in the penultimate prediagnostic sample was 1.556 nmol/L (0.600 to 1.802). This was significantly different from asbestos-exposed controls without malignancy (P less than 0.0001).
  • Among people with a sample within 6 months of diagnosis, 7 of 43 (16%) were mesothelin positive.
  • Comparing the penultimate sample with each person's own earlier samples, mesothelin rose above that person's baseline in 33 of 82 analyzable people who developed mesothelioma.
  • New pain at the time of sampling, but not weight loss or shortness of breath, was significantly associated with elevated mesothelin.
  • Time from sampling to diagnosis was not a significant determinant of mesothelin status (odds ratio 1.011; 95% CI 0.98 to 1.04).
  • Overall, the authors described mesothelin as elevated in between 15% and 40% of individuals before diagnosis, in a population with a high pretest probability of mesothelioma.
• The authors' conclusion: The authors concluded that mesothelin was elevated before diagnosis in between 15% and 40% of this high-risk group. They said many factors need to be addressed before large-scale mesothelin testing is encouraged, including acceptable false-positive and false-negative rates and their financial and psychological costs.
• Limitations the authors state:
  • The study did not take into account the kidney function of healthy subjects, which can affect mesothelin results.
  • Each person's samples were run on the same day. Variation between assay runs could be much higher in a real screening program.
  • Statistical variation is amplified in people with low baseline mesothelin levels.
  • Storage at minus 80°C for more than 10 years could have affected mesothelin concentrations.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

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, Discovery, Biomarker, Mesothelioma, Wittenoom, MESOMARK® Assay, Asbestos Exposure.

Related studies

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• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Early detection of malignant pleural mesothelioma through measurement of soluble mesothelin-related protein and positron emission tomography — E.L. O'Lone, E.K. Park, et al. (2009)
• Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma — K. Shiomi, Y. Hagiwara, 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)
• Sensitivity of urinary mesothelin in patients with malignant mesothelioma — J. Creaney, A.W. Musk, et al. (2010)

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