Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers

  • Michael K. Felten
  • Khaled Khatab
  • Lars Knoll
  • Thomas Schettgen
  • Hendrik Müller-Berndorff
  • Thomas Kraus
Original Article

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Mesothelioma Biomarker Marker velocity Early detection 

References

  1. Creaney J, Robinson BW (2009) Serum and pleural fluid biomarkers for mesothelioma. Curr Opin Pulm Med 15:366–370CrossRefGoogle Scholar
  2. Creaney J, Olsen NJ, Brims F, Dick IM, Musk AW, de Klerk NH, Skates SJ, Robinson BW (2010) Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma. Cancer Epidemiol Biomarkers Prev 19:2238–2246CrossRefGoogle Scholar
  3. 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
  4. Cristaudo A, Bonotti A, Simonini S, Vivaldi A, Guglielmi G, Ambrosino N, Chella A, Lucchi M, Mussi A, Foddis R (2011) Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma. J Thorac Oncol 6:1587–1593CrossRefGoogle Scholar
  5. Felten MK, Knoll L, Eisenhawer C, Ackermann D, Khatab K, Hudepohl J, Zschiesche W, Kraus T (2010) Retrospective exposure assessment to airborne asbestos among power industry workers. J Occup Med Toxicol 5:15CrossRefGoogle Scholar
  6. Grigoriu BD, Scherpereel A, Devos P, Chahine B, Letourneux M, Lebailly P, Gregoire M, Porte H, Copin MC, Lassalle P (2007) Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment. Clin Cancer Res 13:2928–2935CrossRefGoogle Scholar
  7. 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
  8. Henderson DW, Rodelsperger K, Woitowitz HJ, Leigh J (2004) After Helsinki: a multidisciplinary review of the relationship between asbestos exposure and lung cancer, with emphasis on studies published during 1997–2004. Pathology 36:517–550CrossRefGoogle Scholar
  9. Ho M, Bera TK, Willingham MC, Onda M, Hassan R, Fitzgerald D, Pastan I (2007) Mesothelin expression in human lung cancer. Clin Cancer Res 13:1571–1575CrossRefGoogle Scholar
  10. 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
  11. 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
  12. McIntosh MW, Urban N, Karlan B (2002) Generating longitudinal screening algorithms using novel biomarkers for disease. Cancer Epidemiol Biomarkers Prev 11:159–166Google Scholar
  13. Neragi-Miandoab S (2006) Multimodality approach in management of malignant pleural mesothelioma. Eur J Cardiothorac Surg 29:14–19CrossRefGoogle Scholar
  14. Park EK, Thomas PS, Johnson AR, Yates DH (2009) Osteopontin levels in an asbestos-exposed population. Clin Cancer Res 15:1362–1366CrossRefGoogle Scholar
  15. 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
  16. Pass HI, Lott D, Lonardo F, Harbut M, Liu Z, Tang N, Carbone M, Webb C, Wali A (2005) Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med 353:1564–1573CrossRefGoogle Scholar
  17. Pass HI, Wali A, Tang N, Ivanova A, Ivanov S, Harbut M, Carbone M, Allard J (2008) Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions. Ann Thorac Surg 85:265–272 (discussion 272)CrossRefGoogle Scholar
  18. Roberts HC, Patsios DA, Paul NS, Deperrot M, Teel W, Bayanati H, Shepherd F, Johnston MR (2009) Screening for malignant pleural mesothelioma and lung cancer in individuals with a history of asbestos exposure. J Thorac Oncol 4:620–628CrossRefGoogle Scholar
  19. Robinson BW, Creaney J, Lake R, Nowak A, Musk AW, de Klerk N, Winzell P, Hellstrom KE, Hellstrom I (2003) Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 362:1612–1616CrossRefGoogle Scholar
  20. Robinson BW, Musk AW, Lake RA (2005) Malignant mesothelioma. Lancet 366:397–408CrossRefGoogle Scholar
  21. 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
  22. Roe OD, Creaney J, Lundgren S, Larsson E, Sandeck H, Boffetta P, Nilsen TI, Robinson B, Kjaerheim K (2008) Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study. Lung Cancer 61:235–243CrossRefGoogle Scholar
  23. Scherpereel A, Lee YC (2007) Biomarkers for mesothelioma. Curr Opin Pulm Med 13:339–443CrossRefGoogle Scholar
  24. Scherpereel A, Grigoriu B, Conti M, Gey T, Gregoire M, Copin MC, Devos P, Chahine B, Porte H, Lassalle P (2006) Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma. Am J Respir Crit Care Med 173:1155–1160CrossRefGoogle Scholar
  25. Schneider J, Hoffmann H, Dienemann H, Herth FJ, Meister M, Muley T (2008) Diagnostic and prognostic value of soluble mesothelin-related proteins in patients with malignant pleural mesothelioma in comparison with benign asbestosis and lung cancer. J Thorac Oncol 3:1317–1324CrossRefGoogle Scholar
  26. Stewart DJ, Edwards JG, Smythe WR, Waller DA, O’Byrne KJ (2004) Malignant pleural mesothelioma—an update. Int J Occup Environ Health 10:26–39CrossRefGoogle Scholar
  27. 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
  28. Teschke K, Olshan AF, Daniels JL, de Roos AJ, Parks CG, Schulz M, Vaughan TL (2002) Occupational exposure assessment in case-control studies: opportunities for improvement. Occup Environ Med 59:575–593 (discussion 594)CrossRefGoogle Scholar
  29. Vickers AJ, Savage C, O’Brien MF, Lilja H (2009) Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol 27:398–403CrossRefGoogle Scholar
  30. Weber DG, Johnen G, Taeger D, Weber A, Gross IM, Pesch B, Kraus T, Bruning T, Gube M (2010) Assessment of confounding factors affecting the tumor markers SMRP, CA125, and CYFRA21-1 in serum. Biomark Insights 5:1–8CrossRefGoogle Scholar
  31. Weill H, Hughes JM, Churg AM (2004) Changing trends in US mesothelioma incidence. Occup Environ Med 61:438–441CrossRefGoogle Scholar
  32. Zervos MD, Bizekis C, Pass HI (2008) Malignant mesothelioma 2008. Curr Opin Pulm Med 14:303–309CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Michael K. Felten
    • 1
  • Khaled Khatab
    • 1
  • Lars Knoll
    • 1
  • Thomas Schettgen
    • 1
  • Hendrik Müller-Berndorff
    • 1
  • Thomas Kraus
    • 1
  1. 1.Medical Faculty, Institute of Occupational and Social MedicineRWTH Aachen UniversityAachenGermany

Personalised recommendations