Diagnostic accuracy of calretinin for malignant mesothelioma in serous effusions: a meta-analysis

Our plain-English summary of Diagnostic accuracy of calretinin for malignant mesothelioma in serous effusions: a meta-analysis, by D. Li, B. Wang, H. Long, et al (Scientific Reports, 2015).

The study

• Authors: D. Li, B. Wang, H. Long, F. Wen
• Journal: Scientific Reports
• Published: 2015;5:9507
• Type of article: Meta-analysis
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Numerous studies have investigated the utility of calretinin in differentiating malignant mesothelioma (MM) from metastatic carcinoma (MC) in serous effusions. However, the results remain controversial. The aim of this study is to determine the overall accuracy of calretinin in serous effusions for MM through a meta-analysis of published studies. Publications addressing the accuracy of calretinin in the diagnosis of MM were selected from the Medline (Ovid), PubMed, the Cochrane Library Database and the Web of Science. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Statistical analysis was performed by Meta-Disc 1.4 and STATA 12.0 softwares. 18 studies met the inclusion criteria and the summary estimating for calretinin in the diagnosis of MM were: sensitivity 0.91 (95%CI: 0.87-0.94), specificity 0.96 (95%CI: 0.95-0.96), positive likelihood ratio (PLR) 14.42 (95%CI: 7.92-26.26), negative likelihood ratio (NLR) 0.1 (95%CI: 0.05-0.2) and diagnostic odds ratio 163.03 (95%CI: 54.62-486.63). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.92; the area under the curve was 0.97. Our findings suggest that calretinin may be a useful diagnostic tool for confirming MM in serous effusions.

In plain English

This was a meta-analysis, a study that pooled results from earlier published research. The authors searched medical databases up to December 31, 2013 for studies testing whether staining fluid cells for a protein called calretinin could tell malignant mesothelioma apart from metastatic carcinoma (cancer spread from elsewhere) in serous effusions, which are fluid collections in the body cavities. They included 18 studies from 7 countries, covering 2276 individuals. The article did not study asbestos exposure. Pooled across all studies, sensitivity (the share of mesothelioma cases the test flagged) was 0.91 (95% CI 0.87–0.94). Specificity (the share of carcinoma cases correctly testing negative) was 0.96 (95% CI 0.95–0.96). The area under the curve was 0.97. In 7 studies of pleural effusions alone, sensitivity was lower, at 0.84 (95% CI 0.76–0.91). The authors concluded that calretinin may be a useful adjunct to conventional diagnostic tools, to be interpreted alongside histological assessment and clinical findings. They noted that only published studies were included and that smaller studies appeared to overestimate accuracy.

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: Meta-analysis (systematic pooling) of published diagnostic accuracy studies
• Who was studied: 18 published studies from 7 countries, with 2276 individuals in total (study sizes ranged from 30 to 1158, average 126). The studies covered serous effusion specimens from patients with malignant mesothelioma or metastatic carcinoma. Databases were searched up to December 31, 2013, and only full-text papers in English and Chinese were included.
• Exposure: No asbestos or fiber exposure was studied. The study examined a diagnostic test: calretinin immunostaining of effusion cells, on cell blocks or smears, used to distinguish malignant mesothelioma from metastatic carcinoma.
• Main results:
  • Across all 18 studies, pooled sensitivity was 0.91 (95% CI 0.87–0.94) and pooled specificity was 0.96 (95% CI 0.95–0.96).
  • Across all studies, the positive likelihood ratio was 14.42 (95% CI 7.92–26.26) and the negative likelihood ratio was 0.1 (95% CI 0.05–0.2).
  • Across all studies, the pooled diagnostic odds ratio was 163.03 (95% CI 54.62–486.63).
  • Across all studies, the Q-value (maximum joint sensitivity and specificity) was 0.92 and the area under the summary ROC curve was 0.97.
  • In studies using nuclear staining as the cut-off (14 studies in the text, 13 in Table 3), pooled sensitivity was 0.94 (95% CI 0.89–0.97) and pooled specificity was 0.94 (95% CI 0.91–0.95).
  • In the 7 studies of pleural effusions, summary sensitivity was 0.84 (95% CI 0.76–0.91) and specificity was 0.96 (95% CI 0.95–0.97). The authors described this as slightly lower accuracy than the overall analysis.
  • Results varied between studies. None of the factors tested (method, sample size, geographic location, quality score) was found to be a significant source of this variation.
  • The funnel plot showed no obvious asymmetry. The authors interpreted this as no evidence of publication bias.
• The authors' conclusion: The authors concluded that calretinin may be a useful adjunct to conventional diagnostic tools for differentiating malignant mesothelioma from metastatic carcinoma. In their view it should be interpreted in parallel with histological assessment and clinical findings when confirming a diagnosis.
• Limitations the authors state:
  • Only published studies were included. Excluding unpublished data, ongoing studies, conference abstracts and letters may have led to publication bias.
  • Small studies appeared to overestimate calretinin's true diagnostic accuracy.
  • Misclassification was possible, because some adenocarcinomas were diagnosed from the clinical course alone rather than by histology.
  • The included studies used different cut-off values, which made it difficult to determine an optimal cut-off.
  • Because of limited data, the authors could not pool results for peritoneal or pericardial mesothelioma.
  • The authors could not assess effects of laboratory factors, expertise, patient spectrum, setting, or study design such as blinding.

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: Calretinin, Mesothelioma, Meta-Analysis, Carcinoma, Odds Ratio.

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• Performance of the Monoclonal Antibody B72.3 in Diagnosis of Malignant Carcinomatous Serous Effusions-A Systematic Review and Meta-Analysis of Diagnostic Performance — A.H. Lin, M. Hsu, et al. (2025)
• 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)
• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• Calretinin. A selective marker of normal and neoplastic mesothelial cells in serous effusions — M.C. Barberis, M. Faleri, et al. (1997)

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