Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA

Our plain-English summary of Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA, by R. Filiberti, S. Parodi, R. Libener, et al (Medical Oncology, 2013).

The study

• Authors: R. Filiberti, S. Parodi, R. Libener, G.P. Ivaldi, P.A. Canessa, D. Ugolini, B. Bobbio, P. Marroni
• Journal: Medical Oncology
• Published: 2013;30(2):543
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

CYFRA 21-1 and CEA have been applied for the differential diagnosis of malignant pleural mesothelioma (MPM). The soluble mesothelin-related peptide (SMRP) has been proposed as a specific marker for distinguishing MPM from benign diseases and other malignancies in pleural effusions (PEs). In this study, we evaluated the usefulness of SMRP in PEs in the detection of mesotheliomas by comparing it with that of CYFRA 21-1, CEA, and with cytological examination. One hundred and seventy-seven consecutive patients (57 MPM, 64 metastatic tumors, and 56 benign diseases) were evaluated using commercial tests. The performance of the markers was analyzed by standard ROC analysis methods, using the area under a ROC curve (AUC) as a measure of accuracy. CYFRA 21-1 better differentiated malignant from benign effusions. The corresponding area under the receiver operating characteristic curve was 0.87, while it was 0.74 for SMRP and 0.64 for CEA (p < 0.001). Conversely, SMRP differentiated MPM from all other PEs better than both CYFRA 21-1 and CEA (AUC = 0.84, 0.76, and 0.32, respectively, p = 0.003). Low levels of CEA were associated with a MPM diagnosis. The AUC for differentiating MPM from metastases was 0.81 for SMRP, 0.61 for CYFRA 21-1, and 0.20 for CEA (p < 0.001). In cases with negative or suspicious cytology, SMRP and CYFRA 21-1 identified 36/71 and 46/66 malignant PEs (29 and 31 MPM, respectively). Only 1 MPM showed a high CEA concentration. No single marker showed the best performance in any comparison. Results suggest that SMRP could improve CYFRA 21-1 and CEA accuracy in the differential diagnosis of MPM.

In plain English

The authors measured three markers, SMRP (soluble mesothelin-related peptide), CYFRA 21-1 and CEA, in pleural fluid (fluid around the lungs). The fluid came from 177 consecutive patients at two pulmonary departments in Northern Italy, 2009 to 2011. Of these, 57 had malignant pleural mesothelioma, 64 metastatic tumors and 56 benign conditions. Accuracy was measured as the area under a ROC curve (AUC). For telling malignant from benign fluid, CYFRA 21-1 scored highest (AUC 0.87, against 0.74 for SMRP and 0.64 for CEA). For telling mesothelioma from all other fluids, SMRP scored highest (0.84, against 0.76 for CYFRA 21-1), and low CEA levels were associated with mesothelioma. Against metastatic tumors alone, the AUCs were 0.81 for SMRP, 0.61 for CYFRA 21-1 and 0.20 for CEA. Cytology (examining cells in the fluid) had a sensitivity of 41% for all malignant effusions and 33% for mesothelioma. Where cytology was negative or suspicious, SMRP flagged 36 of 71 malignant fluids and CYFRA 21-1 flagged 46 of 66. The authors concluded that no single marker performed best in every comparison, and that SMRP can add information, particularly for separating mesothelioma from 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 accuracy study comparing pleural fluid tumor markers and cytology in consecutive patients, analyzed with ROC curves
• Who was studied: 177 consecutive patients with pleural effusions admitted for diagnosis to two pulmonary departments in Northern Italy, 2009 to 2011: 57 malignant pleural mesothelioma, 64 metastatic tumors, 56 benign effusions. Patients with prior chemotherapy were excluded.
• Exposure: Asbestos exposure was not assessed or reported for these patients. The study measured SMRP (Mesomark ELISA), CYFRA 21-1 and CEA in pleural fluid and compared them with cytology.
• Main results:
  • Malignant versus benign effusions: AUC 0.87 for CYFRA 21-1, 0.74 for SMRP and 0.64 for CEA. CYFRA 21-1 had the highest performance (p less than 0.001).
  • Mesothelioma versus all other effusions: AUC 0.84 for SMRP and 0.76 for CYFRA 21-1. At the best cut-off, sensitivity and specificity were 74% and 86% for SMRP, and 91% and 60% for CYFRA 21-1.
  • CEA had an AUC of 0.32 for mesothelioma versus all other effusions, meaning low CEA levels were associated with a mesothelioma diagnosis.
  • Mesothelioma versus metastatic effusions: AUC 0.81 for SMRP, 0.61 for CYFRA 21-1 and 0.20 for CEA.
  • Cytology alone had a sensitivity of 41% for all malignant effusions and 33% for mesothelioma. With negative and suspicious cases pooled, its specificity was 98%.
  • In patients with negative or suspicious cytology, SMRP identified 36/71 (50.7%) malignant effusions, 29 of them mesothelioma. CYFRA 21-1 identified 46/66 (69.7%) malignant effusions, 31 of them mesothelioma.
  • Among patients with negative or suspicious cytology, CEA was above the cut-off in 17/68 (25%) malignancies, including one mesothelioma.
  • Among benign effusions, 3 of 56 (5.4%) had SMRP above the 12 nmol/l threshold, and 8 (14.3%) had elevated CYFRA 21-1.
• The authors' conclusion: The authors concluded that no single marker had the best performance in every comparison. CYFRA 21-1 and CEA may help when cytology is inconclusive, and SMRP can add information to support the other markers and to better separate mesothelioma from non-mesothelioma malignancies.
• Limitations the authors state:
  • The small number of sarcomatoid mesotheliomas did not allow conclusions about mesothelin levels in that subtype.

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, Differential Diagnosis, Pleural Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Pleural Effusion, Mesothelioma, Cytology.

Related studies

• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)
• Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma — J. Creaney, A. Segal, et al. (2014)
• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)
• Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study — O.D. Roe, J. Creaney, et al. (2008)
• Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin — G. Ak, Y. Tada, et al. (2017)

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