Markers for the non-invasive diagnosis of mesothelioma: a systematic review

Our plain-English summary of Markers for the non-invasive diagnosis of mesothelioma: a systematic review, by S. van der Bij, E. Schaake, H. Koffijberg, et al (British Journal of Cancer, 2011).

The study

• Authors: S. van der Bij, E. Schaake, H. Koffijberg, J.A. Burgers, B.A. de Mol, K.G. Moons
• Journal: British Journal of Cancer
• Published: 2011;104(8):1325-33
• Type of article: Systematic review
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Numerous markers have been evaluated to facilitate the non-invasive diagnostic work-up of mesothelioma. The purpose of this study was to conduct a structured review of the diagnostic performance of non-invasive marker tests for the detection of mesothelioma in patients with suspected mesothelioma.

Methods: Studies on the diagnostic accuracy of serum and cytological markers published till 31 December 2009, available in either PUBMED or Embase, to detect or exclude the presence of mesothelioma were extracted. Study quality was assessed with use of the Quadas criteria.

Results: In total, 82 articles were included in this systemic review. Overall, quality of the incorporated studies to address our objective was poor. The most frequently studied immunohistochemical markers for cytological analysis were EMA, Ber-Ep4, CEA, and calretinin. The most frequently investigated serum marker was soluble mesothelin-related protein (SMRP). The markers CEA, Ber-EP4, and calretinin were most valuable in discriminating mesothelioma from other malignant diseases. Markers EMA and SMRP were most valuable in discriminating mesothelioma from non-malignant diseases. No marker performed well in discriminating between mesothelioma and all other diseases.

Conclusion: Currently, there is only limited evidence to properly assess the value of non-invasive marker tests in the diagnosis of mesothelioma. Studies were of limited value to address our objective and results showed considerable unexplained study heterogeneity.

In plain English

This article was a systematic review. It covered published studies, up to 31 December 2009, on how accurately non-invasive tests could detect or rule out mesothelioma. These tests measured markers in blood serum or in pleural or peritoneal fluid, stained cells in that fluid, or looked at genes. The authors included 82 articles and judged their quality as generally poor. Only three selected a representative group of consecutive patients suspected of having mesothelioma. CEA, Ber-EP4 and calretinin appeared most useful for telling mesothelioma apart from other cancers. EMA and the blood marker SMRP appeared most useful for telling it apart from non-cancerous conditions. No marker performed well against all other diseases. SMRP levels were lower in sarcomatoid mesothelioma. Because the included studies were of low quality, the authors did not pool their results. The authors concluded that there was only limited evidence to properly judge these tests. They named SMRP, CEA, EMA, calretinin and Ber-EP4 as markers for further validation.

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: Systematic review of diagnostic accuracy studies; results were not pooled in a meta-analysis
• Who was studied: 82 published articles up to 31 December 2009: 36 on serum or effusion markers, 41 on immunohistochemical markers, 2 on genetic markers and 3 on several types of markers. Each included study had at least 10 mesothelioma patients.
• Exposure: Asbestos exposure was not studied. What was assessed was non-invasive marker tests in four groups: serum markers; pleural and peritoneal fluid markers; immunohistochemical markers used on cells in fluid samples; and genetic markers.
• Main results:
  • The quality of the included studies was generally poor.
  • Only three articles adequately selected a representative group of consecutive patients suspected of mesothelioma. Nearly all studies (88%) were affected by disease-verification bias.
  • The reviewed studies covered 54 immunohistochemical markers, 21 serum markers, 12 effusion markers and 1 genetic marker.
  • CEA, Ber-EP4 and calretinin appeared most valuable for distinguishing mesothelioma from other cancers.
  • EMA and SMRP appeared most valuable for distinguishing mesothelioma from non-cancerous diseases.
  • No marker performed well at distinguishing mesothelioma from all other diseases.
  • For SMRP in serum, differences between studies appeared to be largely explained by the different cut-off values each study used. SMRP levels were lower in sarcomatoid mesothelioma than in other types (data not shown).
  • For CEA in fluid compared against other cancers, specificity ranged across studies from 43% (95% CI 33 to 54) to 88% (95% CI 69 to 96). CEA levels below 40 ng per ml were compatible with both non-malignancy and mesothelioma.
  • For calretinin, sensitivity ranged from 85 to 100% across studies, except in one study.
  • EMA staining was positive in 73 to 100% of mesothelioma patients and in 91 to 100% of other cancers. In four studies, a membranous EMA staining pattern was seen mainly in mesothelioma (55 to 92%) and in under 20% of other cancers.
  • Two studies tested calretinin and CEA on the same patients, comparing mesothelioma with other cancers. Specificity was 100% for calretinin and about 58% for CEA in both. Sensitivities were 91 and 100% for calretinin, and 100% in both studies for CEA.
  • No robust conclusion could be drawn on how markers compared with each other, because study methods differed widely and results were heterogeneous.
• The authors' conclusion: The authors concluded that there is currently only limited evidence to properly assess the value of non-invasive marker tests in diagnosing mesothelioma. They wrote that SMRP alone did not yet seem accurate enough, and that SMRP, CEA, EMA, calretinin and Ber-EP4 warranted further validation.
• Limitations the authors state:
  • Because the included studies were of low quality, the authors chose not to pool sensitivities and specificities.
  • Low quality and poor reporting meant the authors could not explore why results differed between studies.
  • Only single markers were assessed, not combinations of markers.
  • Unpublished studies were not searched for, so the results may be affected by publication bias.
  • Studies that did not report how many patients fell above or below a cut-off value could not be included.
  • Most immunohistochemical studies included only epithelioid and biphasic mesotheliomas. The authors noted that sarcomatoid mesothelioma sheds almost no cells into fluid.
  • Most studies did not consider what immunohistochemical staining adds beyond how the cells look under the microscope.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Systematic Review, Ber-EP4, Calretinin, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP).

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