Diagnostic value of D2-40 immunostaining for malignant mesothelioma: a meta-analysis

Our plain-English summary of Diagnostic value of D2-40 immunostaining for malignant mesothelioma: a meta-analysis, by C. He, B. Wang, C. Wan, et al (Oncotarget, 2017).

The study

• Authors: C. He, B. Wang, C. Wan, T. Yang, Y. Shen
• Journal: Oncotarget
• Published: 2017;8(38):64407-64416
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) has become a global disease burden for its rising incidence and invariable fatality. D2-40 has been widely used as an immunostaining marker of diagnosing MM, while its diagnostic value has not yet been evaluated. Our study aimed to assess the overall accuracy of D2-40 immunostaining for diagnosing MM through a meta-analysis. A total of 22 studies with 2,264 participants were identified from PubMed, EMBASE, Web of Science, Scopus and the Cochrane database. The pooled sensitivity and specificity of D2-40 for MM was 0.86 (95% CI: 0.84-0.89) and 0.77 (95% CI: 0.74-0.79), respectively. The area under the summary receiver operating characteristic curve is 0.93, with a diagnostic odds ratio 40.37 (95% CI: 19.97-81.61). None of the study variates was found to be a source of heterogeneity after meta-regression analysis. In conclusion, D2-40 immunostaining may not give sufficient evidence by itself to diagnose MM and should be in combination with other markers to improve the accuracy of diagnosis.

In plain English

This was a meta-analysis, a study that pools the results of earlier studies. The authors searched five databases through 2016 for studies of how well D2-40, an antibody stain, identifies malignant mesothelioma. They included 22 studies from 8 countries with 2,264 participants: 862 mesothelioma cases and 1,402 comparison cases, most often lung carcinoma. The study did not examine asbestos exposure. Pooled across studies, D2-40 detected 86% of mesotheliomas (sensitivity 0.86, 95% CI 0.84 to 0.89) and correctly gave a negative result in 77% of comparison cases (specificity 0.77, 95% CI 0.74 to 0.79). It performed better for epithelioid mesothelioma (sensitivity 0.92, 95% CI 0.89 to 0.94) than for sarcomatoid mesothelioma (sensitivity 0.65, 95% CI 0.56 to 0.73). For pleural mesothelioma, sensitivity was 0.85 (95% CI 0.82 to 0.88) and specificity 0.81 (95% CI 0.78 to 0.84). Results varied widely between studies, and the authors could not identify why. The authors concluded D2-40 may not be accurate enough to diagnose mesothelioma alone and should be combined with other markers. They noted that strict inclusion criteria left only a small set of studies.

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 literature search and meta-analysis of diagnostic accuracy studies
• Who was studied: 22 published studies, found in PubMed, EMBASE, Web of Science, Scopus and the Cochrane database up to December 31, 2016. The studies came from 8 countries and covered 2,264 participants: 862 malignant mesothelioma cases and 1,402 controls. Lung carcinoma made up 778 of the 1,402 controls. Four studies used cell blocks from effusions and 18 used tissue.
• Exposure: No asbestos exposure was studied. The study evaluated a diagnostic laboratory test, D2-40 antibody immunostaining, for diagnosing malignant mesothelioma.
• Main results:
  • All 22 studies combined: pooled sensitivity of D2-40 for malignant mesothelioma was 0.86 (95% CI 0.84 to 0.89) and pooled specificity was 0.77 (95% CI 0.74 to 0.79). The area under the summary ROC curve was 0.93.
  • All studies combined: pooled diagnostic odds ratio was 40.37 (95% CI 19.97 to 81.61), which the authors described as a modest level of overall accuracy. The pooled positive likelihood ratio was 5.15 and the pooled negative likelihood ratio was 0.18.
  • The authors interpreted the pooled sensitivity and specificity as a missed-diagnosis rate of 14% and a misdiagnosis rate of 23% for D2-40.
  • Epithelioid mesothelioma subgroup (16 studies, 540 cases, 1,020 controls): sensitivity 0.92 (95% CI 0.89 to 0.94), specificity 0.84, area under the curve 0.96.
  • Sarcomatoid mesothelioma subgroup (10 studies, 131 cases, 659 controls): pooled sensitivity was lower, at 0.65 (95% CI 0.56 to 0.73), with specificity 0.84 and area under the curve 0.83. The authors found D2-40 performed better for epithelioid and biphasic mesothelioma than for sarcomatoid mesothelioma.
  • Pleural mesothelioma subgroup (13 studies, 536 cases, 707 controls): sensitivity 0.85 (95% CI 0.82 to 0.88), specificity 0.81 (95% CI 0.78 to 0.84), area under the curve 0.93.
  • There was high heterogeneity among studies (for example, I2 of 82.8% for sensitivity and 93.1% for specificity). Meta-regression on eight study characteristics did not identify any of them as a source of the heterogeneity.
  • Deeks' funnel plot test gave P = 0.48, which the authors read as a low likelihood of publication bias.
• The authors' conclusion: The authors concluded that D2-40 immunostaining may not be accurate enough to diagnose malignant mesothelioma alone. They said its results should be interpreted together with other markers, and that new markers should be explored.
• Limitations the authors state:
  • Strict inclusion criteria meant only a small set of studies could be included.
  • There was substantial heterogeneity across studies, and its source could not be identified.
  • Only 4 studies used cytology of effusions, so the accuracy of cytology-based diagnosis could not be evaluated accurately.
  • Staining procedures were not uniform: antibody dilutions ranged from 1:25 to 1:200, and cut-off values for positive staining differed between studies.

Topics

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), Mesothelioma, Meta-Analysis, Odds Ratio.

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