MESOMARK: a potential test for malignant pleural mesothelioma

Our plain-English summary of MESOMARK: a potential test for malignant pleural mesothelioma, by H.L. Beyer, R.D. Geschwindt, C.L. Glover, et al (Clinical Chemistry, 2007).

The study

• Authors: H.L. Beyer, R.D. Geschwindt, C.L. Glover, L. Tran, I. Hellstrom, K.E. Hellstrom, M.C. Miller, T. Verch, W.J. Allard, H.I. Pass, N.Y. Sardesai
• Journal: Clinical Chemistry
• Published: 2007;53(4):666-72
• Cited by: 111 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Soluble mesothelin-related peptides (SMRP)have been reported to be potential biomarkers for malignant pleural mesothelioma (MPM). We report analytical and preliminary clinical studies of MESOMARK, a quantitative assay for SMRP.

Methods: The MESOMARK assay is a 2-step immunoenzymatic assay in an ELISA format with a 6-point calibration curve (0-32 nmol/L). We assessed analytical imprecision, analyte stability, and analytical interferences. We measured SMRP by this assay in 409 apparently healthy individuals (reference interval study), 177 patients with nonmalignant conditions, and 500 cancer patients, including 88 with MPM.

Results: The limit of detection was 0.16 nmol/L. At 2-19 nmol/L, intraassay imprecision (CV) was 1.1%-5.3%, and total imprecision was 4.0%-11.0%. The mean dilution recovery for 5 samples was 109% (range, 99%-113%). No interference was seen from added bilirubin (200 mg/L), hemoglobin (500 mg/L), triglycerides (30 g/L), chemotherapeutic agents, or other tested substances. Recombinant mesothelin was stable in serum upon freeze/thaw at -70 degrees C and upon storage for at least 7 days at 2-8 degrees C. The 99(th) percentile of the reference group was 1.5 nmol/L [95% confidence interval (CI), 1.2-1.6 nmol/L; n = 409], and mean SMRP was significantly higher in sera from patients with MPM (7.5 nmol/L; 95% CI, 2.8-12.1 nmol/L; n = 88). SMRP was increased in 52% and 5% of MPM patients and asbestos-exposed individuals, respectively. Concentrations in other nonmalignant and malignant conditions were similar to those in healthy controls.

Conclusions: The MESOMARK assay is analytically robust and may be useful for the detection and management of mesothelioma.

In plain English

This laboratory and preliminary clinical study evaluated MESOMARK, a blood test for soluble mesothelin-related peptides (SMRP), proposed as a marker for malignant pleural mesothelioma. In laboratory checks, the test could detect levels as low as 0.16 nmol/L. With added bilirubin, triglycerides, chemotherapy drugs and other substances, mean results were 96% to 101% of expected values. The authors then measured SMRP in 409 apparently healthy volunteers, 88 patients with histologically confirmed mesothelioma, 61 asbestos-exposed individuals and patients with other conditions. The 99th percentile in healthy volunteers, 1.5 nmol/L (95% confidence interval 1.2 to 1.6), served as the cutoff. SMRP was above this cutoff in 52% of mesothelioma patients and 5% of asbestos-exposed individuals. In 83% of lung cancer samples SMRP was below the cutoff. Levels showed no clear relationship to mesothelioma stage or histologic type. Fiber types and exposure levels for the asbestos-exposed group were not described. The authors concluded that SMRP is higher in mesothelioma patients than in healthy people and can be reliably measured. They noted it can also rise in renal failure, hypertension and some other tumors, and they called the study preliminary.

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: Analytical (laboratory) validation and preliminary clinical evaluation of a blood test (diagnostic assay), using retrospectively collected serum samples
• Who was studied: Serum from 409 apparently healthy volunteers; 88 patients with histologically confirmed mesothelioma, seen at the Karmanos Cancer Institute and operated on there or at the National Cancer Institute between 1995 and 2003; 61 asbestos-exposed individuals; 111 ovarian, 174 lung, 50 colon, 52 pancreatic and 25 endometrial cancer patients; 100 people with hypertension and 16 with endometriosis. Samples other than the mesothelioma and asbestos-exposed samples were obtained from commercial sources in 2004.
• Exposure: The study measured SMRP in blood with the MESOMARK assay. No asbestos fiber types, products, jobs or doses were reported. The asbestos-exposed group was described only as patients seen at the Center for Environmental Medicine in Southfield, Michigan.
• Main results:
  • In laboratory testing, the limit of detection was 0.16 nmol/L.
  • After potential interfering substances were added to serum samples, mean results were 96% to 101% of the expected values. Individual ranges in Table 1 were wider, for example 85% to 110% for cisplatin.
  • In the 409 apparently healthy volunteers, the 99th percentile of SMRP was 1.5 nmol/L (95% CI 1.2–1.6 nmol/L). This value was used as the cutoff.
  • Mean SMRP in the 88 mesothelioma patients was 7.5 nmol/L (95% CI 2.8–12.1 nmol/L). In the healthy volunteers the mean was 0.4 nmol/L (SD 0.4), according to Table 2.
  • SMRP was increased (above the 1.5 nmol/L cutoff) in 52% of mesothelioma patients and in 5% of the 61 asbestos-exposed individuals.
  • SMRP was below the cutoff in 83% of samples from the 174 lung cancer patients and in 95% of samples from asbestos-exposed individuals.
  • Comparing healthy volunteers with preoperative mesothelioma samples, the area under the ROC curve was 87.4% (95% CI 82.8%–92.0%).
  • Comparing asbestos-exposed patients with preoperative mesothelioma samples, the area under the ROC curve was 80.6% (95% CI 73.7%–87.4%).
  • At the 1.5 nmol/L cutoff, Table 4 reported a sensitivity for detecting mesothelioma of 57% (95% CI 46%–67%).
  • Among the mesothelioma patients, SMRP results showed no clear relationship to stage or histologic type.
• The authors' conclusion: The authors concluded that serum SMRP is higher in mesothelioma patients than in healthy persons and can be reliably measured by the MESOMARK assay. They also concluded that the assay may be useful for the detection and management of mesothelioma.
• Limitations the authors state:
  • The authors stated that SMRP is increased in patients with renal failure, hypertension and certain other tumors such as ovarian cancer.
  • The authors stated that, because mesothelioma is rare, using SMRP for screening may require adding other markers to increase specificity.
  • The authors described the study as preliminary and said other studies were under way to confirm its diagnostic accuracy.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Biomarker, MESOMARK® Assay, Mesothelin, confidence interval, Mesothelioma.

Related studies

• A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma — I. Raiko, H.P. Rihs, et al. (2017)
• Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma — K. Shiomi, Y. Hagiwara, et al. (2008)
• Soluble mesothelin-related protein--a blood test for mesothelioma — B.W. Robinson, J. Creaney, et al. (2005)
• Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin — K. Iwahori, T. Osaki, et al. (2008)
• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2010)
• Soluble mesothelin-related peptides (SMRP) - high stability of a potential tumor marker for mesothelioma — D.G. Weber, D. Taeger, et al. (2007)

Browse return to medical research.