Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma

Our plain-English summary of Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma, by A. Scherpereel, B. Grigoriu, M. Conti, et al (American Journal of Respiratory and Critical Care Medicine, 2006).

The study

• Authors: A. Scherpereel, B. Grigoriu, M. Conti, T. Gey, M. Grégoire, M.C. Copin, P. Devos, B. Chahine, H. Porte, P. Lassalle
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 2006;173(10):1155-60
• Cited by: 174 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin-related peptides (SMRPs) and osteopontin, but no subsequent validation has been published yet.

Methods: We prospectively evaluated SMRPs in serum and pleural effusion from patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35), or benign pleural lesions associated with asbestos exposure (n = 28), recruited when first suspected for mesothelioma.

Findings: Mean serum SMRP level was higher in patients with mesothelioma (2.05 +/- 2.57 nM/L [median +/- interquartile range]) than in patients with metastasis (1.02 +/- 1.79 nM/L) or benign lesions (0.55 +/- 0.59 nM/L). The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off = 1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 +/- 83.2 nM/L; benign lesions: 6.4 +/- 11.1 nM/L; metastasis: 6.36 +/- 21.73 nM/L). The AUC for pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off = 10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP-differentiating metastasis and mesothelioma was 0.793.

Interpretation: We show that SMRPs may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRPs was similar in both types of samples, but pleural fluid SMRPs may better discriminate mesothelioma from pleural metastasis.

In plain English

From May 2003, at 20 hospitals in northern and western France, the authors prospectively recruited 137 patients suspected of, or recently diagnosed with, malignant pleural mesothelioma and measured soluble mesothelin-related peptides (SMRPs) in serum and pleural fluid. Of these, 74 had confirmed mesothelioma, 35 had cancer that had spread to the pleura from elsewhere (metastasis), and 28 had benign pleural lesions associated with asbestos exposure; serum was available for 60, 30 and 23 of them respectively, and pleural fluid for 43, 28 and 21. Median serum SMRP was 2.05 nM/L in the mesothelioma group, 1.02 in the metastasis group and 0.55 in the benign group. At a cut-off of 0.93 nM/L, serum SMRP separated mesothelioma from benign lesions with 80% sensitivity and 82.6% specificity. It separated mesothelioma from metastasis less well. Pleural fluid levels were higher than serum levels in every group. Pleural fluid scored higher than serum for separating mesothelioma from metastasis, but that difference was not statistically significant. Levels were highest in the epithelioid subtype. The authors concluded that pleural fluid SMRP was at least as useful as serum SMRP. They added that biopsy remains the gold standard and that larger studies are needed.

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: Prospective, multicentre diagnostic study measuring a blood and pleural fluid marker
• Who was studied: 137 consecutive patients suspected of, or recently diagnosed with, malignant pleural mesothelioma (MPM), recruited from May 2003 at 20 hospitals in northern and western France. Final diagnoses were 74 MPM, 35 pleural metastasis of carcinomas, and 28 benign pleural lesions associated with asbestos exposure. Serum was available for 60 MPM, 30 metastasis and 23 benign patients. Pleural fluid was available for 43 MPM, 28 metastasis and 21 benign patients.
• Exposure: The quantity studied was the SMRP level in serum and pleural fluid, measured with a commercial ELISA kit (Mesomark). Most patients had documented asbestos exposure: 56 (75.7%) of the MPM group, 22 (78.6%) of the benign group and 9 (25.8%) of the metastasis group. No fiber types were reported.
• Main results:
  • Serum SMRP levels differed between the three groups. Medians were 2.05 nM/L in MPM patients, 1.02 nM/L in metastasis patients and 0.55 nM/L in benign-lesion patients. MPM was significantly higher than both other groups.
  • Serum SMRP, MPM versus benign lesions: AUC 0.872 (0.798 to 0.946). At a cut-off of 0.93 nM/L, sensitivity was 80% and specificity 82.6%.
  • Serum SMRP, MPM versus metastasis: AUC 0.693 (0.576 to 0.810). At a cut-off of 1.85 nM/L, sensitivity was 58.3% and specificity 73.3%.
  • Pleural fluid SMRP values were much higher than serum values in all three groups.
  • Median pleural fluid SMRP was significantly higher in MPM patients (46.1 nM/L) than in metastasis patients (6.36 nM/L) or benign-lesion patients (6.4 nM/L).
  • Pleural fluid SMRP, MPM versus benign lesions: AUC 0.831 (0.734 to 0.927). At a cut-off of 10.4 nM/L, sensitivity was 76.7% and specificity 76.2%.
  • Pleural fluid SMRP, MPM versus metastasis: AUC 0.793 (0.691 to 0.894). No single best cut-off was found.
  • Pleural fluid had a higher AUC than serum for separating MPM from metastasis, but the difference was not statistically significant when only patients with both samples were considered.
  • Combining serum and pleural values gave no statistically significant advantage over either measure alone.
  • Within MPM, median serum SMRP was 2.47 nM/L in the epithelioid subtype (n=42). This was significantly higher than in the mixed subtype (0.892 nM/L, n=9, p value 0.026). The sarcomatoid subtype had 1.05 nM/L (n=5, p value 0.06, which the authors attributed to the low number of patients).
  • Pleural fluid SMRP was also significantly higher in epithelioid mesothelioma than in the sarcomatoid and mixed subtypes.
  • For screening, setting serum sensitivity above 90 to 95% would drop specificity to between 30 and 50%. The authors said serum SMRP may not reach sufficient sensitivity with adequate specificity as a screening marker.
• The authors' conclusion: The authors concluded that the commercial kit performed less well than earlier laboratory tests. They found pleural fluid SMRP at least as useful as serum SMRP and potentially better at separating MPM from metastatic carcinoma. Pathological study of pleural biopsies remains the gold standard, and further studies in larger groups are needed.
• Limitations the authors state:
  • Not all patients had both pleural fluid and serum, so the two were compared in a limited number of patients.
  • The combined serum-plus-pleural analysis was done on only 73 patients.
  • The metastasis comparison group had a lower rate of documented asbestos exposure.

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: Soluble Mesothelin-Related Peptides (SMRP), Pleural Mesothelioma, Mesothelioma, Osteopontin, Pleural Effusion, Metastasis, Carcinoma, Asbestos Exposure.

Related studies

• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure — J.A. Rodríguez Portal, E. Rodríguez Becerra, et al. (2009)
• Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment — B.D. Grigoriu, A. Scherpereel, et al. (2007)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis — L. Luo, H.Z. Shi, 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)

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