Mesothelin-family proteins and diagnosis of mesothelioma

Our plain-English summary of Mesothelin-family proteins and diagnosis of mesothelioma, by B.W. Robinson, J. Creaney, R. Lake, et al (Lancet, 2003).

The study

• Authors: B.W. Robinson, J. Creaney, R. Lake, A. Nowak, A.W. Musk, N. de Klerk, P. Winzell, K.E. Hellstrom, I. Hellstrom
• Journal: Lancet
• Published: 2003;362(9396):1612-6
• Cited by: 421 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Mesothelioma is a highly aggressive tumour for which there are no reliable serum tumour markers. Identification of such a marker would be useful in diagnosis of mesothelioma and for monitoring responses to treatment and screening at-risk individuals.

Methods: We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases.

Findings: 37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma.

Interpretation: Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma.

In plain English

This study tested whether a blood test for soluble mesothelin-related proteins (SMR) could help identify mesothelioma. In Perth, Western Australia, investigators who did not know each person's diagnosis measured SMR in serum from 44 patients with mesothelioma, 160 patients with other lung or pleural diseases or other cancers, 40 healthy asbestos-exposed people and 28 unexposed laboratory staff. The article describes participants' asbestos exposure as coming from the Wittenoom crocidolite operation or downstream industrial use of crocidolite. Raised SMR was found in 37 of the 44 mesothelioma patients (sensitivity 84%, 95% CI 73–93), in none of the 28 unexposed controls, and in 3 of the 160 patients with other diseases. Levels were higher with larger tumours, though 15 of 21 patients with the smallest tumours tested positive. Seven of the 40 asbestos-exposed controls had raised SMR. Three of them later developed mesothelioma and one died of non-small-cell lung cancer. None of the 33 with normal SMR developed mesothelioma or other cancer over 8 years. The authors noted this group was small. They concluded that serum SMR is a useful adjunct in diagnosing mesothelioma.

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: Blinded diagnostic study of a serum marker (soluble mesothelin-related proteins, measured by sandwich ELISA) comparing mesothelioma patients with disease and healthy control groups, with follow-up of asbestos-exposed controls
• Who was studied: 44 patients with mesothelioma (39 men, 5 women) from consecutive patients at respiratory clinics of Sir Charles Gairdner Hospital or Hollywood Specialist Centre, Perth, Western Australia, sampled 1997 to 2002. Comparison groups were 160 patients with other inflammatory or malignant lung and pleural diseases, 40 healthy asbestos-exposed controls in a surveillance programme (1990 to 2001), and 28 healthy laboratory staff with no known asbestos exposure.
• Exposure: Asbestos exposure through the Wittenoom crocidolite operation or downstream use of crocidolite in industry. The measured factor was serum SMR, with a positive value defined as above 0·218, which is 3 SD above the mean absorbance of non-asbestos-exposed healthy controls.
• Main results:
  • 37 of 44 mesothelioma patients had raised SMR, a sensitivity of 84% (95% CI 73–93).
  • Specificity was 100% (91–100) against other pleural diseases (38 of 38), 95% (84–100) against other lung tumours (21 of 22), and 83% (70–93) against other asbestos-exposed people (33 of 40).
  • Among 160 patients with other diseases, SMR was raised in only 3: one of 22 with asbestosis, one of 22 with cryptogenic fibrosing alveolitis-idiopathic pulmonary fibrosis, and one of 22 with non-small-cell lung cancer. None of 7 patients with lung adenocarcinoma had raised SMR.
  • SMR was significantly higher in mesothelioma patients with tumours wider than 3 cm. Sensitivity for the smallest tumours was 71% (15 of 21).
  • In samples taken in the first few months after diagnosis, patients with mainly epithelial tumours had higher SMR than those with mainly sarcomatoid tumours (p=0·0094). By the table, 23 of 25 epithelial and 1 of 4 sarcomatoid cases were SMR positive.
  • In three mesothelioma patients who had surgical debulking, SMR had fallen by 37·7%, 38·4% and 46·8% one month after the procedure.
  • Of 7 asbestos-exposed controls with raised SMR, 3 developed mesothelioma at 15, 26 and 69 months after sampling, and one died of non-small-cell lung cancer 4 years after sampling.
  • None of the 33 asbestos-exposed controls with normal SMR developed mesothelioma or other cancer in 8 years of follow-up. The difference between groups had p=0·007 (Fisher's exact test).
  • Of 8 mesothelioma patients with earlier stored samples, 2 had raised SMR 12–48 months before presentation.
• The authors' conclusion: The authors proposed that measuring serum SMR is a useful adjunct in diagnosing mesothelioma and that serial measurements correlate with tumour bulk. They also suggested SMR should be monitored in at-risk asbestos-exposed individuals to determine whether early intervention improves outcome.
• Limitations the authors state:
  • The asbestos-exposed follow-up group was small.
  • Specificity may fall below 100% in studies that include other tumours that can invade the pleura, such as ovarian, lung and breast carcinomas.
  • P values were not adjusted for multiple comparisons.

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, Mesothelioma, Carcinoma, Disease Progression.

Related studies

• Soluble mesothelin-related protein--a blood test for mesothelioma — B.W. Robinson, J. Creaney, et al. (2005)
• 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 family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results — F. Di Serio, A. Fontana, et al. (2007)
• Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma — J. Creaney, I. van Bruggen, et al. (2007)
• Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study — O.D. Roe, J. Creaney, et al. (2008)
• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)

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