Abstract
Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools – like minimally-invasive biomarkers – are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.
Highlights
Asbestos is still used in many countries despite being classified as a human carcinogen by the International Agency for Research on Cancer (IARC) in 19771,2
During a period of about ten years 2,769 participants of a surveillance program of the German Social Accident Insurance for asbestos workers were recruited at 26 medical centers throughout Germany
The receiver operating characteristic (ROC) analysis of calretinin, mesothelin, and the “best case” scenario from sequential combination of both markers yielded an area under the curve (AUC) of 0.74, 0.66, and 0.83, respectively (Fig. 3)
Summary
Asbestos is still used in many countries despite being classified as a human carcinogen by the International Agency for Research on Cancer (IARC) in 19771,2. We have established an assay for the protein marker calretinin and confirmed the results in independent groups of patients from three continents, using a conventional case-control design[26,27,28]. These studies usually enroll patients with more advanced tumor stages and lack prediagnostic samples to assess the performance of markers to detect tumors prior to the occurrence of clinical symptoms[25]. We established a high-risk cohort of former asbestos workers with annual examinations and blood sampling over a period of ten years. Prediagnostic samples of incident cases were used to evaluate the biomarkers calretinin and mesothelin in a nested case-control design
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