Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine.

Objectives: Calretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics.
Setting: This re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014.
Participants: The present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS.
Primary and Secondary Outcomes: Mesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA.
Results: Compared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA.
Conclusions: The newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.
Competing Interests: Competing interests: The IPA has supplied DLD Diagnostika with the antibodies to produce the Calretinin ELISA kits. In turn, the IPA has received Calretinin ELISA kits at a reduced price and may benefit from future sales of the kits. The IPA has received Mesomark ELISA kits at a reduced price and free Lumipulse G Mesothelin assay reagents for the temporarily provided Lumipulse G600 II instrument from Fujirebio. Otherwise, the individual authors declare no competing interests.
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