Asbestos exposure, pleural mesothelioma, and serum osteopontin levels

Our plain-English summary of Asbestos exposure, pleural mesothelioma, and serum osteopontin levels, by H.I. Pass, D. Lott, F. Lonardo, et al (The New England Journal of Medicine, 2005).

The study

• Authors: H.I. Pass, D. Lott, F. Lonardo, M. Harbut, Z. Liu, N. Tang, M. Carbone, C. Webb, A. Wali
• Journal: The New England Journal of Medicine
• Published: 2005;353(15):1564-73
• Cited by: 297 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: We investigated the presence of osteopontin in pleural mesothelioma and determined serum osteopontin levels in three populations: subjects without cancer who were exposed to asbestos, subjects without cancer who were not exposed to asbestos, and patients with pleural mesothelioma who were exposed to asbestos.

Methods: A group of 69 subjects with asbestos-related nonmalignant pulmonary disease were compared with 45 subjects without exposure to asbestos and 76 patients with surgically staged pleural mesothelioma. Tumor tissue was examined for osteopontin by immunohistochemical analysis, and serum osteopontin levels were measured by an enzyme-linked immunosorbent assay.

Results: There were no significant differences in mean (+/-SE) serum osteopontin levels between age-matched subjects with exposure to asbestos and subjects without exposure to asbestos (30+/-3 ng per milliliter and 20+/-4 ng per milliliter, respectively; P=0.06). In the group with exposure to asbestos, elevated serum osteopontin levels were associated with pulmonary plaques and fibrosis (56+/-13 ng per milliliter) but not with normal radiographic findings (21+/-5 ng per milliliter), plaques alone (23+/-3 ng per milliliter), or fibrosis alone (32+/-7 ng per milliliter) (P=0.004). Serum osteopontin levels were significantly higher in the group with pleural mesothelioma than in the group with exposure to asbestos (133+/-10 ng per milliliter vs. 30+/-3 ng per milliliter, P<0.001). Immunohistochemical analysis revealed osteopontin staining of the tumor cells in 36 of 38 samples of pleural mesothelioma. An analysis of serum osteopontin levels comparing the receiver-operating-characteristic curve in the group exposed to asbestos with that of the group with mesothelioma had a sensitivity of 77.6 percent and a specificity of 85.5 percent at a cutoff value of 48.3 ng of osteopontin per milliliter. Subgroup analysis comparing patients with stage I mesothelioma with subjects with exposure to asbestos revealed a sensitivity of 84.6 percent and a specificity of 88.4 percent at a cutoff value of 62.4 ng of osteopontin per milliliter.

Conclusions: Serum osteopontin levels can be used to distinguish persons with exposure to asbestos who do not have cancer from those with exposure to asbestos who have pleural mesothelioma.

Copyright 2005 Massachusetts Medical Society.

In plain English

This study measured the blood protein osteopontin in three groups. The first was 69 people seen at a Michigan occupational medicine center in 2004 with a history of asbestos exposure, X-ray changes of asbestos-related nonmalignant disease, or both. The second was 45 current or former smokers without known asbestos exposure. The third was 76 pleural mesothelioma patients scheduled for surgery. Average serum osteopontin was 30 ng per milliliter in the exposed group and 20 in the unexposed group, not a statistically significant difference (P=0.06). Among exposed subjects, levels were higher with lung fibrosis and with 10 or more years of exposure. They were highest with both pleural plaques and fibrosis (56 ng per milliliter). Mesothelioma patients averaged 133 ng per milliliter. A cutoff of 48.3 ng per milliliter flagged 77.6 percent of mesothelioma patients, while 85.5 percent of exposed subjects fell below it. Tumor cells stained for osteopontin in 36 of 38 samples. The authors concluded that serum osteopontin could distinguish asbestos-exposed people with pleural mesothelioma from those without cancer. They noted that osteopontin levels are also elevated in other cancers.

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: Diagnostic biomarker study comparing blood (serum) osteopontin levels across three groups to test it as a marker for pleural mesothelioma, with staining of mesothelioma tumor tissue for osteopontin
• Who was studied: Three groups. First, 69 subjects with a history of asbestos exposure, radiographic evidence of asbestosis, or both, enrolled July to September 2004 at the Center for Occupational and Environmental Medicine, Royal Oak, Michigan. Second, 45 current (25) or former (20) smokers aged 33 to 74 with no known asbestos exposure and normal chest radiographs, who were undergoing screening bronchoscopy. Third, 76 patients with pleural mesothelioma scheduled for cytoreductive surgery (13 stage I, 20 stage II, 43 stage III).
• Exposure: Occupational asbestos exposure; fiber types were not specified. In the exposed group, 57 of 69 had worked in an asbestos-related trade for at least five years, 7 for less than five years, and 5 had radiographic abnormalities without documented exposure. Trades included foundry work (11), pipe fitting (7), building and construction (7), brake assembly or repair (5), boiler repair (4), vermiculite insulation exposure (4) and others. In the mesothelioma group, exposure was documented by occupational history in 59 of 76 patients.
• Main results:
  • Mean serum osteopontin in the asbestos-exposed group was 30±3 ng per milliliter (range 2 to 221). This did not differ significantly from the unexposed group (20±4 ng per milliliter, P=0.06).
  • Within the exposed group, those with lung fibrosis had a higher mean osteopontin level than those without fibrosis (43 vs 23 ng per milliliter, P=0.004). Levels did not differ significantly by presence or absence of pleural plaques (P=0.88).
  • Within the exposed group, mean levels were higher with 10 or more years of exposure than with fewer than 10 years (34 vs 16 ng per milliliter, P=0.02).
  • Among exposed subjects, levels were lower with a normal chest radiograph (21±5), plaques (23±3) or fibrosis (32±7) than with both plaques and fibrosis (56±13 ng per milliliter, P=0.004).
  • In a multiple regression analysis of the exposed group, duration of asbestos exposure and radiographic findings were the factors independently associated with osteopontin levels.
  • Mean serum osteopontin in the pleural mesothelioma group was 133±10 ng per milliliter, compared with 30±3 ng per milliliter in the asbestos-exposed group (P<0.001).
  • Among mesothelioma patients, mean levels did not differ significantly by stage: stage I 147±26, stage II 158±22, stage III 118±12 ng per milliliter (P>0.15). Each stage differed significantly from the exposed group.
  • Comparing all 76 mesothelioma patients with the 69 exposed subjects, the area under the ROC curve (a measure of how well the test separates the groups) was 0.888 (95 percent confidence interval 0.826 to 0.934).
  • A cutoff of 48.3 ng per milliliter gave a sensitivity of 77.6 percent and a specificity of 85.5 percent for separating mesothelioma patients from exposed subjects.
  • Comparing the 13 stage I mesothelioma patients with the 69 exposed subjects, the area under the ROC curve was 0.906.
  • For stage I mesothelioma versus exposed subjects, the most accurate cutoff was 62.4 ng per milliliter, with a sensitivity of 84.6 percent and a specificity of 88.4 percent.
  • Tumor tissue was available from 38 of the 76 mesothelioma patients, and 36 of those 38 samples stained positive for osteopontin.
• The authors' conclusion: The authors concluded that serum osteopontin levels can be used to distinguish asbestos-exposed persons who do not have cancer from asbestos-exposed persons who have pleural mesothelioma. In the discussion, they made this claim specifically for early pleural mesothelioma, regardless of the tumor's histologic type.
• Limitations the authors state:
  • The authors stated that the apparent ability of the test to identify stage I mesothelioma still needed to be confirmed.
  • Osteopontin levels are also elevated in other cancers, including gastrointestinal, laryngeal and urinary cancers.
  • The authors stated that their data do not justify using osteopontin measurements in people other than those exposed to asbestos as defined in the study or those with radiographic evidence of pleural disease.
  • Only 38 of the 76 tumor samples could be stained for osteopontin, because the other 38 were unavailable.
  • Because of technical differences in the assay and the use of serum rather than plasma, the measured levels were lower than the manufacturer's standard plasma levels and differed from levels in other studies.

Topics

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

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

Related studies

• Serum osteopontin levels--is it time to screen asbestos-exposed workers for pleural mesothelioma? — M.R. Cullen (2005)
• Asbestos exposure and serum osteopontin — A.W. O'Regan, D. Serlin, et al. (2006)
• Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system — D. Vordermark, H.M. Said, et al. (2006)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma — A. Scherpereel, B. Grigoriu, et al. (2006)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)

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