Mesothelin family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results

Our plain-English summary of Mesothelin family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results, by F. Di Serio, A. Fontana, M. Loizzi, et al (Clinical Chemistry and Laboratory Medicine, 2007).

The study

• Authors: F. Di Serio, A. Fontana, M. Loizzi, G. Capotorto, P. Maggiolini, E. Mera, L. Bisceglia, R. Molinini
• Journal: Clinical Chemistry and Laboratory Medicine
• Published: 2007;45(5):634-8
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Studies have suggested that soluble mesothelin-related protein (SMRP) can be used as a serum marker of malignant mesothelioma.

Methods: We assessed the analytical performance of the Mesomark (Fujirebio Diagnostic) two-step ELISA on an automated analyser and performed a preliminary clinical evaluation. The precision of the assay and the in vitro effect of interfering substances on SMRP concentrations were investigated. The serum marker was analysed in 109 healthy subjects never exposed to asbestos, 26 healthy subjects exposed to asbestos, 33 patients with asbestosis, 33 with asbestos-related pleural plaques, 10 with non-malignant pleural diseases, 30 with lung cancer and 24 with histological diagnosis of pleural mesothelioma.

Results: Using the International Mesothelioma Interest Group classification, there were nine stage IV, two stage III, four stage II and nine stage I patients. SMRP concentrations of 4.75, 11.0 and 14 nmol/mL showed a total imprecision of 3.5%, 3.1% and 3.8%. The detection limit was 0.035 nmol/mL; the mean SMRP concentration of 0.63 nmol/mL was associated with a coefficient of variation of 10%. There was no effect (p>0.05) of interfering substances. Serum samples from patients with established pleural mesothelioma had significantly higher (p<0.05) concentrations of SMRP than control healthy and patient groups.

Conclusions: SMRP measured on automated systems could be useful for the diagnosis of mesothelioma in routine clinical practice.

In plain English

This laboratory study in Bari, Italy, tested the Mesomark blood test for soluble mesothelin-related protein (SMRP) on an automated analyser, with a preliminary clinical evaluation. Total imprecision was 3.1% to 3.8% for materials at 4.75 to 14.0 nmol/mL. It rose to 10% at 0.63 nmol/mL (95% CI 0.58 to 0.68) and 20% at 0.2 nmol/mL (95% CI 0.17 to 0.22). Results were linear from 0 to 32 nmol/mL, with no significant interference from added bilirubin, fats or haemoglobin. SMRP was measured in 109 never-exposed and 26 asbestos-exposed healthy people, 33 patients with asbestosis, 33 with asbestos-related pleural plaques, 10 with non-malignant pleural disease, 30 with lung cancer and 24 with pleural mesothelioma. The mesothelioma group's geometric mean, 2.2 nmol/mL (95% CI 1.43 to 3.46), differed statistically from all other groups. At 1.5 nmol/mL, 16 of 24 mesothelioma patients tested positive (sensitivity 67%, 95% CI 41.7 to 84.3%). Specificity was 92.5% (95% CI 85.1 to 96.9%) against asbestos-exposed healthy people and asbestos-related disease patients combined. The authors concluded the method suits clinical laboratory use. They cautioned about small numbers and low sensitivity, calling for longitudinal studies.

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: Analytical (laboratory performance) evaluation of an automated blood test, plus a preliminary clinical comparison of SMRP levels across groups using leftover serum samples
• Who was studied: 135 healthy subjects: 109 never exposed to asbestos and 26 asbestos-exposed with no CT evidence of asbestos-related disease or mesothelioma. 66 patients with asbestos-related diseases (33 asbestosis, 33 asbestos-related pleural plaques) from an occupational medicine surveillance program. 64 consecutive thoracic surgery patients: 10 with non-malignant pleural diseases with effusions, 30 with lung cancer and 24 with pleural mesothelioma (20 epithelioid, 2 sarcomatoid, 2 mixed). All were at the University Hospital of Bari, Italy. Dates of sample collection are not stated.
• Exposure: Asbestos exposure was used only to define groups. Fiber types, jobs and exposure levels are not reported. The test studied was the Mesomark two-step ELISA for SMRP, run on a DSX Dynex automated analyser.
• Main results:
  • Analytical performance: the detection limit was 0.035 nmol/mL. Total imprecision was 3.5%, 3.1% and 3.8% for materials with mean SMRP of 4.75, 11.0 and 14.0 nmol/mL.
  • Precision was poorer at low concentrations. Mean SMRP of 0.63 nmol/mL (95% CI 0.58–0.68) was associated with a CV of 10%, and 0.2 nmol/mL (95% CI 0.17–0.22) with a CV of 20%.
  • The method was linear from 0 to 32 nmol/mL. Added bilirubin, lipids (triglycerides) and haemoglobin produced no statistically significant interference.
  • Mesothelioma patients (n=24) had a geometric mean SMRP of 2.2 nmol/mL (95% CI 1.43–3.46). The geometric means in the other groups were 0.68 (non-exposed healthy), 0.73 (asbestos-exposed healthy), 0.81 (asbestosis), 0.82 (pleural plaques), 0.74 (non-malignant pleural disease) and 1.0 (lung cancer) nmol/mL. Mesothelioma values were statistically different (p less than 0.05) from all other groups.
  • Mean SMRP was 4.5 nmol/mL in epithelioid mesothelioma (n=20), 1.0 nmol/mL in the sarcomatoid subtype (n=2) and 1.3 nmol/mL in the mixed subtype (n=2). The authors also reported that epithelioid levels were significantly higher than in lung adenocarcinoma (1.7 nmol/mL, n=7).
  • At a cutoff of 1.5 nmol/mL, the authors compared mesothelioma patients with at-risk subjects (asbestos-exposed healthy people and patients with asbestos-related diseases). Sensitivity was 67% (95% CI 41.7–84.3%) and specificity 92.5% (95% CI 85.1–96.9%). The positive predictive value was 69.6% and the negative predictive value 91.5%. There were 16 true positives, 8 false negatives, 86 true negatives and 7 false positives. The area under the ROC curve was 0.817 (95% CI 0.73–0.88).
• The authors' conclusion: The authors concluded that the automated Mesomark method is suitable for use in the clinical laboratory. They said their preliminary clinical results confirm a potential role for serum SMRP in diagnosing mesothelioma. They also said the marker should be validated through prospective clinical trials.
• Limitations the authors state:
  • The findings on mesothelioma subtypes and lung adenocarcinoma are limited by the small number of samples.
  • Sensitivity was low (67%), so negative test results should be interpreted with caution.
  • Longitudinal studies are needed before routine use, including studies of whether SMRP tracks disease activity or predicts mesothelioma in exposed people.
  • Current results do not allow a cost/benefit assessment of the marker.

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

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