Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma

Our plain-English summary of Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma, by K. Shiomi, Y. Hagiwara, K. Sonoue, et al (Clinical Cancer Research, 2008).

The study

• Authors: K. Shiomi, Y. Hagiwara, K. Sonoue, T. Segawa, K. Miyashita, M. Maeda, H. Izumi, K. Masuda, M. Hirabayashi, T. Moroboshi, T. Yoshiyama, A. Ishida, Y. Natori, A. Inoue, M. Kobayashi, Y. Sakao, H. Miyamoto, K. Takahashi, O. Hino
• Journal: Clinical Cancer Research
• Published: 2008;14(5):1431-7
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Because mesothelioma initially progresses on the surface of the pleura and peritoneum without forming masses, it has been difficult to diagnose at an early stage. It would be very useful to identify a tumor marker that could be used for screening to enable more diagnoses to be made at an early, treatable stage.

Materials And Methods: We had previously identified N-ERC/mesothelin as a potential biomarker for mesothelioma. In the current work, we used a newly developed ELISA system to gain data on N-ERC/mesothelin levels in various clinical settings. A total of 102 healthy volunteers were recruited. In addition, 39 patients were diagnosed with mesothelioma, 53 patients were diagnosed with diseases that should be distinguished from mesothelioma, and 201 subjects were diagnosed with asbestos-related nonmalignant diseases (including simple exposure to asbestosis) who were treated at any of the cooperating hospitals were enrolled.

Results: Serum N-ERC/mesothelin levels measured by a new ELISA system showed that the median values from patients with mesothelioma were extremely high compared with levels obtained from other patients. Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially. In four important models of clinical settings, the sensitivity and specificity of N-ERC/mesothelin were about 71% to 90% and 88% to 93%, respectively.

Conclusion: N-ERC/mesothelin is a very promising tumor marker for mesothelioma, especially epithelioid mesothelioma.

In plain English

This Japanese study developed a new blood test (an ELISA) for N-ERC/mesothelin, a protein fragment the authors proposed as a blood marker for mesothelioma, and compared it with their earlier version of the test. Levels were measured in 102 healthy volunteers and in 293 patients enrolled prospectively at cooperating hospitals from August 2005 through October 2006: 39 with mesothelioma, 201 with asbestos exposure or nonmalignant asbestos-related disease (pleural plaque, benign asbestos pleuritis or asbestosis), 45 with lung cancer and 8 with other conditions. In healthy volunteers, levels did not differ significantly by sex or smoking status but rose with age. Median levels in mesothelioma patients were extremely high compared with other patients, and levels were significantly higher in epithelioid mesothelioma than in other types (P = 0.039). In four clinical scenarios, sensitivity was about 71% to 90% and specificity about 88% to 93%; the new test did better than the old one in every scenario. The authors concluded that N-ERC/mesothelin shows promise as a tumor marker for mesothelioma, especially the epithelioid type.

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: Laboratory development of a new blood test (sandwich ELISA) for N-ERC/mesothelin, followed by a prospective multicenter study of its diagnostic accuracy compared with the authors' previous ELISA
• Who was studied: 102 healthy volunteers and 293 patients treated at cooperating hospitals in Japan from August 2005 through October 2006. The patients were 39 with mesothelioma (21 epithelioid, 9 biphasic, 9 sarcomatous), 98 with pleural plaque, 83 with asbestos exposure, 14 with benign asbestos-related pleuritis, 6 with asbestosis, 45 with lung cancer (including 8 with carcinomatous pleuritis) and 8 with other conditions.
• Exposure: This study tested a blood marker, not asbestos exposure itself. One comparison group (201 people) had asbestos exposure or nonmalignant asbestos-related disease (pleural plaque, benign asbestos pleuritis, asbestosis). No fiber types, jobs or doses were reported.
• Main results:
  • Among healthy volunteers, serum N-ERC/mesothelin levels did not differ significantly by sex (P = 0.96) or smoking status (P = 0.87).
  • Among healthy volunteers, serum levels increased with age (P = 0.013).
  • Median serum levels in patients with mesothelioma were extremely high compared with levels in the other patient groups.
  • Serum levels were significantly higher in epithelioid-type mesothelioma than in the other histologic types (P = 0.039).
  • In patients with epithelioid mesothelioma, levels tended to rise as stage increased.
  • Across four clinical scenarios (screening at-risk patients and distinguishing mesothelioma from other conditions, each done for all mesothelioma and for epithelioid mesothelioma), sensitivity was about 71% to 90% and specificity about 88% to 93%.
  • In all four scenarios, the area under the curve was higher for the new ELISA than for the previous one.
  • In the few monitoring samples available from mesothelioma patients, levels appeared to vary with tumor volume.
• The authors' conclusion: The authors concluded that their new ELISA is more sensitive than the previous system, and that N-ERC/mesothelin shows promise as a tumor marker for mesothelioma, especially the epithelioid type.
• Limitations the authors state:
  • Only a few samples were available to assess the test's value for monitoring patients with mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Tumor Marker, Mesothelioma, Pleura, Peritoneum, Biomarker, Epithelioid.

Related studies

• Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients — I. Raiko, I. Sander, et al. (2010)
• Establishment of a novel specific ELISA system for rat N- and C-ERC/mesothelin. Rat ERC/mesothelin in the body fluids of mice bearing mesothelioma — Y. Hagiwara, Y. Hamada, et al. (2008)
• Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin — K. Iwahori, T. Osaki, et al. (2008)
• Soluble mesothelin-related peptides (SMRP) - high stability of a potential tumor marker for mesothelioma — D.G. Weber, D. Taeger, et al. (2007)
• Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic markers — M. Maeda, O. Hino (2006)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)

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