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

Our plain-English summary of Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers, by M.K. Felten, K. Khatab, L. Knoll, et al (International Archives of Occupational and Environmental Health, 2014).

The study

• Authors: M.K. Felten, K. Khatab, L. Knoll, T. Schettgen, H. Müller-Berndorff, T. Kraus
• Journal: International Archives of Occupational and Environmental Health
• Published: 2014;87(2):195-204
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This German study measured two proposed blood tumour markers, mesothelin and osteopontin, in 2,262 volunteers sampled between October 2005 and May 2009: 1,894 formerly asbestos-exposed power industry workers, 266 people with an unknown asbestos history, and 102 unexposed controls. Fiber types were not reported. Exposure duration came from a self-completed questionnaire. Older age was associated with higher levels of both markers, while exposure duration showed no effect in regression models. Some exposed workers' levels rose more than 10% over at least a year without a diagnosis of mesothelioma or lung cancer. Among them, the 95th percentile of the annual rise was 0.402 nmol/l for mesothelin (290 workers) and 334 ng/ml for osteopontin (81 workers). Sixteen exposed workers developed malignant pleural mesothelioma (5) or lung cancer (11). At the first test, only one of them had a mesothelin result above the cut-off, and none had an osteopontin result above it. The two mesothelioma patients tested repeatedly before diagnosis showed a steep mesothelin rise. The authors concluded that fixed cut-off values appeared inadequate for these markers. They cautioned that case numbers were small and follow-up was short.

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: Mainly cross-sectional, non-randomized study with repeated (longitudinal) blood tests in the asbestos-exposed subgroup
• Who was studied: 2,262 volunteers sampled October 2005 to May 2009, with blood tested at the Institute of Occupational and Social Medicine in Aachen, Germany. The groups were 1,894 formerly asbestos-exposed power industry workers, 266 people from health institutions with an unknown asbestos history, and 102 non-exposed controls from an occupational health clinic.
• Exposure: Former occupational asbestos exposure in the power industry. Duration was self-reported by questionnaire, and fiber types were not specified. Average exposure duration was 19.5 years (mesothelin analysis group) and 19.6 years (osteopontin analysis group).
• Main results:
  • Across the whole cohort, age had a strong effect on both markers, with higher concentrations at older ages.
  • In regression models, exposure duration showed no effect on marker levels (mesothelin p = 0.08; osteopontin p = 0.09). A simple correlation was significant only for osteopontin.
  • Some exposed workers had four tests and did not develop lung cancer or mesothelioma (mesothelin n = 55, osteopontin n = 63). In this group, mean mesothelin did not change significantly. Mean osteopontin in tests three (p = 0.002) and four (p = 0.001) was significantly lower than at baseline.
  • 290 exposed workers (15% of 1,884) had a mesothelin increase of more than 10% over at least 365 days without a diagnosis of MPM or lung cancer. Their mean annual increase was 0.172 nmol/l (SD 0.271), and the 95th percentile was 0.402 nmol/l.
  • 81 exposed workers (4% of 1,876) met the same criteria for osteopontin. Their mean annual increase was 86 ng/ml (SD 103), and the 95th percentile was 334 ng/ml.
  • Within this rising-mesothelin group, the annual mesothelin increase was significantly higher in workers with benign asbestos-related lesions of lung or pleura (BLLP, n = 131): 0.227 nmol/l, compared with 0.126 nmol/l in those without (p = 0.004). BLLP made no difference to the annual osteopontin increase.
  • By the end of follow-up, 16 exposed workers had developed MPM (n = 5) or lung cancer (n = 11). Five of them had already been diagnosed at the initial blood test.
  • At the initial test, only one of these 16 patients (mm4) had a mesothelin result above the cut point, and all osteopontin results were below the cut point.
  • The two MPM patients with repeated tests before diagnosis (mm4 and mm5) showed a steep mesothelin increase, and both reached extreme levels. No clear pattern was seen for osteopontin or for mesothelin in the lung cancer patients.
• The authors' conclusion: The authors concluded that age strongly influenced both markers, while exposure duration and benign pleural disease had no effect in their cohort. They reported some indications that mesothelin may rise 6 to 18 months before clinical symptoms of MPM. In their view, fixed cut-off values appeared inadequate for these markers, and the rate of change ('marker velocity') or person-specific approaches should be researched further.
• Limitations the authors state:
  • Some cancer cases may not have been reported, and follow-up was short, so case numbers should be interpreted with caution.
  • The number of malignancies was probably too small for valid conclusions.
  • The three subgroups had different characteristics.
  • There were no data on kidney (renal) function.
  • Exposure data were self-assessed and could not be validated.
  • The retesting protocol (early repeat test after a high result) probably created a bias.
  • BLLP was not subdivided, so rates of lung asbestosis or diffuse pleural thickening could not be assessed.
  • Information on smoking habits was limited and often unreliable.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Osteopontin, Pleural Mesothelioma, Lung Cancer, Asbestos Exposure.

Related studies

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• Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma — I. Pantazopoulos, P. Boura, et al. (2013)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Mesothelin and osteopontin — I. Pantazopoulos, T. Xanthos, et al. (2013)
• Mesothelin and osteopontin — G. Hillerdal (2013)

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