Combination of mesothelin and CEA significantly improves the differentiation between malignant pleural mesothelioma, benign asbestos disease, and lung cancer

Our plain-English summary of Combination of mesothelin and CEA significantly improves the differentiation between malignant pleural mesothelioma, benign asbestos disease, and lung cancer, by T. Muley, H. Dienemann, F.J. Herth, et al (Journal of Thoracic Oncology, 2013).

The study

• Authors: T. Muley, H. Dienemann, F.J. Herth, M. Thomas, M. Meister, J. Schneider
• Journal: Journal of Thoracic Oncology
• Published: 2013;8(7):947-51
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Soluble mesothelin-related peptides (SMRP) have been reported as potential markers for the diagnosis of malignant pleural mesothelioma (MPM). We wondered, whether a combination with a carcinoembryonic antigen (CEA) test might improve the relatively low diagnostic yield of the SMRP test.

Methods: In a retrospective study, SMRP (mesothelin) and CEA serum concentrations were measured, using commercially available kits, in 93 previously untreated MPM patients, 75 patients with benign asbestos disease, and 139 patients suffering from lung cancer (LC).

Results: The differentiation between MPM, LC, and benign asbestos disease could be improved by applying the ratio mesothelin/CEA. Whereas CEA expression was found to be low in MPM, most LC patients had elevated CEA serum levels. The area under curve (AUC) of the receiver operator characteristics curve for mesothelin alone was found to be only 0.708. For mesothelin/CEA the AUC of the receiver operator characteristics curve increased to 0.978. The sensitivity was 93% (69%) at 95% (100%) specificity for the differentiation between MPM and LC. Comparison of MPM and benign asbestos disease showed that the AUC was 0.887 and the sensitivity 56% (47%) at 95% (100%) specificity. In contrast, the AUC for the mesothelin test alone was only 0.715, and for the CEA test alone it was 0.16. An average increment in sensitivity of 38% (range, 16%-63%) could be achieved by the quotient mesothelin/CEA compared with the sensitivity of mesothelin alone.

Conclusion: The diagnostic yield of the mesothelin test can be considerably improved when combined with a CEA test with regard to the differential diagnosis between MPM and LC and between MPM and benign asbestos disease.

In plain English

This retrospective study, by researchers in Heidelberg and Giessen, Germany, tested whether combining two blood tests could help tell malignant pleural mesothelioma (MPM) apart from lung cancer and from benign asbestos-related disease. The authors measured serum mesothelin (also called SMRP) and carcinoembryonic antigen (CEA) in 93 previously untreated MPM patients, 139 lung cancer patients and 75 patients with benign asbestos disease. They then divided mesothelin by CEA. Median mesothelin was 1.4 nmol/L in MPM, 0.9 nmol/L in benign asbestos disease and 0.8 nmol/L in lung cancer. CEA was highest in lung cancer and lowest in MPM. Test accuracy was measured as the area under the curve, where a higher value means the test separated the groups better. For MPM versus lung cancer it was 0.987 for the ratio (the abstract prints 0.978), against 0.708 for mesothelin alone. For MPM versus benign asbestos disease it was 0.887, against 0.715 for mesothelin alone. At 95% specificity, the ratio identified 93% of MPM patients when compared with lung cancer and 56% when compared with benign disease. The authors concluded that the ratio made the differential diagnosis easier.

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: retrospective diagnostic study comparing blood test (biomarker) levels between patient groups
• Who was studied: 93 previously untreated patients with malignant pleural mesothelioma (87 men, 6 women), 139 patients with newly diagnosed primary lung cancer, and 75 patients with benign asbestos-related disease (19 with pleural plaques, 49 with hyalinosis complicata or rounded atelectasis, 7 with lung asbestosis). Serum samples were collected between 1998 and 2005. The authors work in Heidelberg and Giessen, Germany.
• Exposure: No asbestos exposure or fiber type was measured. The study measured two blood markers, serum mesothelin (SMRP) and CEA, using commercial test kits, and the ratio of mesothelin to CEA.
• Main results:
  • Mesothelin was significantly higher in MPM patients than in benign asbestos disease patients and lung cancer patients (p less than 0.0001 for each).
  • Median mesothelin: 1.4 nmol/L in MPM, 0.9 nmol/L in benign asbestos disease, 0.8 nmol/L in lung cancer.
  • CEA levels were highest in lung cancer (median 3.9 ng/ml), then benign asbestos disease (1.4 ng/ml), then MPM (0.3 ng/ml).
  • MPM versus lung cancer: the area under the curve for the mesothelin/CEA ratio was 0.987 in the results section (0.978 in the abstract).
  • MPM versus lung cancer: the area under the curve was 0.708 for mesothelin alone and 0.011 for CEA alone.
  • MPM versus benign asbestos disease: the area under the curve was 0.887 for the ratio and 0.715 for mesothelin alone.
  • MPM versus lung cancer: using the ratio, sensitivity was 93% at 95% specificity and 69% at 100% specificity.
  • MPM versus benign asbestos disease: using the ratio, sensitivity was 56% at 95% specificity and 47% at 100% specificity.
  • Compared with mesothelin alone, the ratio raised sensitivity by an average of 38% (range 16% to 63%).
• The authors' conclusion: The authors concluded that combining mesothelin and CEA as a ratio made it easier to tell apart mesothelioma, lung cancer and benign asbestos disease. They recommended using both tests for diagnosis and differential diagnosis.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Pleural Mesothelioma, Lung Cancer, Soluble Mesothelin-Related Peptides (SMRP), Carcinoembryonic Antigen (CEA), Differential Diagnosis.

Related studies

• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)
• Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma — L. Santarelli, S. Staffolani, et al. (2015)
• Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma — B.M. Burt, H.S. Lee, et al. (2017)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study — F. Bruno, D. Baratti, et al. (2018)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)

Browse more research in Journal of Thoracic Oncology, or return to medical research.