Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers
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In patients developing malignant pleural mesothelioma (MPM) or lung cancer, using effective tumour markers is the quickest way to ensure early diagnosis and improve survival time. The aim of our study was to assess the influence of age and asbestos exposure on the blood levels of the proposed tumour markers, mesothelin and osteopontin, and to determine the change of these markers over time.
We analysed 3,329 blood samples of 2,262 participants including 1,894 formerly asbestos-exposed power industry workers, a mixed group of 266 participants with an unknown history of asbestos exposure and a group of 102 non-asbestos-exposed controls. Marker concentrations were determined using commercial ELISA kits.
While age had a strong influence on marker levels, there was no association between exposure duration or benign asbestos-related disease and marker levels. In order to assess the maximum increase that can be expected to occur in asbestos-exposed workers those with an at least 10 % increase were selected (n = 290 for mesothelin and n = 81 for osteopontin). The 95th percentile of the annual change was 0.402 nmol/l for mesothelin and 334 ng/ml for osteopontin. In two patients with MPM and five with lung cancer, we could obtain more than one marker result before the diagnosis was made. Both MPM patients showed a steep increase of mesothelin levels.
Fixed cut-off values for deciding between intensive clinical work-up and continued surveillance appeared inadequate for the evaluated markers. While general conclusions cannot be drawn, we can say that the results of the two patients would be consistent with a mesothelin increase between 6 and 18 months before clinical symptoms developed.
KeywordsMesothelioma Biomarker Marker velocity Early detection
The authors wish to thank Dr. Christian Feldhaus and Dr. Hans Joachim Majunke of RWE Power AG, Essen, Dr. Nicola Kotschy-Lang of Berufsgenossenschaftliche Klinik für Berufskrankheiten, Falkenstein, and PD Dr. Wolfgang Zschiesche and Dr. Johannes Hüdepohl of the German Social Accident Insurance Institution for the energy, textile, electrical and media products sectors (BGETEM), Cologne, for their support in building the cohort and collecting a large proportion of the blood samples. We are also grateful to Kathy Bischof for reviewing the manuscript. The study was supported by unrestricted grants to the University Hospital Aachen from the German Social Accident Insurance Institution for the energy, textile, electrical and media products sectors (BGETEM, grant number 360057) and the company RWE Power AG (grant number 370221).
Conflict of interest
The authors declare that they have no conflict of interest.
- Cristaudo A, Foddis R, Vivaldi A, Guglielmi G, Dipalma N, Filiberti R, Neri M, Ceppi M, Paganuzzi M, Ivaldi GP, Mencoboni M, Canessa PA, Ambrosino N, Chella A, Mutti L, Puntoni R (2007) Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer. Clin Cancer Res 13:5076–5081CrossRefGoogle Scholar
- Grigoriu BD, Grigoriu C, Chahine B, Gey T, Scherpereel A (2009) Clinical utility of diagnostic markers for malignant pleural mesothelioma. Monaldi Arch Chest Dis 71:31–38Google Scholar
- Hollevoet K, van Cleemput J, Thimpont J, de Vuyst P, Bosquee L, Nackaerts K, Germonpre P, Vansteelandt S, Kishi Y, Delanghe JR, van Meerbeeck JP (2011) Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study. J Thorac Oncol 6:889–895CrossRefGoogle Scholar
- Lowe KA, Shah C, Wallace E, Anderson G, Paley P, McIntosh M, Andersen MR, Scholler N, Bergan L, Thorpe J, Urban N, Drescher CW (2008) Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 17:2480–2487CrossRefGoogle Scholar
- McIntosh MW, Urban N, Karlan B (2002) Generating longitudinal screening algorithms using novel biomarkers for disease. Cancer Epidemiol Biomarkers Prev 11:159–166Google Scholar
- Park EK, Thomas PS, Creaney J, Johnson AR, Robinson BW, Yates DH (2010) Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population. Clin Chem Lab Med 48:869–874Google Scholar
- Rodriguez Portal JA, Rodriguez Becerra E, Rodriguez Rodriguez D, Alfageme Michavila I, Quero Martinez A, Diego Roza C, Leon Jimenez A, Isidro Montes I, Cebollero Rivas P (2009) Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure. Cancer Epidemiol Biomarkers Prev 18:646–650CrossRefGoogle Scholar
- Sugarbaker DJ, Flores RM, Jaklitsch MT, Richards WG, Strauss GM, Corson JM, Decamp MM Jr, Swanson SJ, Bueno R, Lukanich JM, Baldini EH, Mentzer SJ (1999) Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 117:54–63 (discussion 63–65)CrossRefGoogle Scholar