Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study

Our plain-English summary of Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study, by E.K. Park, A. Sandrini, D.H. Yates, et al (American Journal of Respiratory and Critical Care Medicine, 2008).

The study

• Authors: E.K. Park, A. Sandrini, D.H. Yates, J. Creaney, B.W. Robinson, P.S. Thomas, A.R. Johnson
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 2008;178(8):832-7
• Cited by: 80 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Rationale: Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown.

Objectives: We aimed to evaluate SMRP in an asbestos-exposed cohort.

Methods: A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography.

Measurements And Main Results: Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01).

Conclusions: This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

In plain English

This prospective cohort study measured a blood marker, soluble mesothelin-related protein (SMRP), in 538 people with asbestos or other dust exposure. They attended routine screening and compensation examinations at the Workers' Compensation (Dust Diseases) Board of New South Wales, Sydney, Australia, between January and November 2006, and were followed for 12 months. The aim was to test SMRP as a screening tool for malignant mesothelioma. Fifteen subjects (2.8%) had levels of 2.5 nM or greater and were investigated with scans. One had lung cancer, which was removed by surgery. None showed evidence of mesothelioma, and no subject was diagnosed with mesothelioma during the study. Two subjects who died of cancer, one of lung cancer and one of pancreatic cancer, had levels below the cutoff. Subjects without asbestos-related disease had lower mean SMRP than subjects with pleural plaques alone. The authors concluded that SMRP is unlikely to prove useful for screening. They noted several probable false positives, follow-up of only one year, and that participants were not randomly selected.

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: prospective cohort study
• Who was studied: 538 subjects with successful blood collection (529 male, 9 female) out of 621 who agreed, from a potential total of 1,315. All attended the Workers' Compensation (Dust Diseases) Board of New South Wales, Sydney, Australia, for routine screening and compensation examinations between January and November 2006.
• Exposure: Occupational asbestos exposure, plus some workers with other dust exposures (including a silicosis group). The article does not name fiber types.
• Main results:
  • Mean SMRP in asbestos-exposed subjects with no apparent asbestos-related disease (n=223) was 0.79 nM (SD 0.45). In subjects with pleural plaques alone (n=142) it was 1.06 nM (SD 0.92). The lower level in the first group was statistically significant (P less than 0.01).
  • 15 of 538 subjects (2.8%) had SMRP of 2.5 nM or greater and were classed as abnormal.
  • Among those with elevated SMRP, one lung cancer (an adenocarcinoma) was detected and resected.
  • Of the 14 elevated-SMRP subjects who had PET/CT scans, none had evidence of mesothelioma. Four had abnormal scans: one cardiac abnormality, possibly a left atrial tumor, which the subject declined to investigate further, and three with hilar lymphadenopathy. Two of the three had follow-up CTs showing no malignancy, and one declined further investigation.
  • No subject in the cohort was diagnosed with mesothelioma.
  • Six subjects died during the study. The subject who died of lung cancer had SMRP of 1.14 nM, and the one who died of pancreatic carcinoma had 0.79 nM. Both were below the 2.5 nM cutoff, so neither cancer was detected by SMRP.
  • If the lower thresholds used in other studies (0.9 and 1.5 nM) had been applied, 210 and 61 subjects respectively would have been classed as abnormal.
  • The authors described several of the elevated results as probable false positives, a classification that could change with further follow-up.
• The authors' conclusion: The authors concluded that, on their data to date, SMRP is unlikely to prove useful for screening for mesothelioma in asbestos-exposed people, and is less useful than in diagnosing mesothelioma in symptomatic patients. They expected the false-positive rate of SMRP screening to be high.
• Limitations the authors state:
  • Follow-up was limited to 1 year, so the authors considered it premature to calculate sensitivity and specificity. The true incidence of mesothelioma and other cancers in the cohort is not yet known.
  • Subjects were not randomly selected from the general population and were being assessed for compensation, so they are a biased group.
  • The higher SMRP in subjects with pleural plaques may be a type II error, or may reflect occult disease that will appear on future follow-up.

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, Cohort Study, Soluble Mesothelin-Related Peptides (SMRP), Malignant Mesothelioma, Lung Cancer, Pleural Plaques.

Related studies

• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)
• 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)
• Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure — J.A. Rodríguez Portal, E. Rodríguez Becerra, et al. (2009)
• Soluble mesothelin-related protein--a blood test for mesothelioma — B.W. Robinson, J. Creaney, et al. (2005)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma — A. Scherpereel, B. Grigoriu, et al. (2006)

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