Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma

Our plain-English summary of Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma, by J. Creaney, A. Segal, N. Olsen, et al (Disease Markers, 2014).

The study

• Authors: J. Creaney, A. Segal, N. Olsen, I.M. Dick, A.W. Musk, S.J. Skates, B.W. Robinson
• Journal: Disease Markers
• Published: 2014;2014:413946
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Rationale: The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain.

Objectives: To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM.

Methods And Measurements: Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined.

Results: 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy.

Conclusions: A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis.

In plain English

This Western Australian study asked whether measuring a protein called mesothelin in fluid around the lungs (pleural effusion) helps diagnose pleural malignant mesothelioma. The authors tested 2156 effusion samples from 1331 people, sent for cell examination (cytology) between 2005 and 2010. Final diagnoses were 183 mesothelioma, 436 other cancers and 712 non-cancerous effusions. Using each person's most recent sample and counting a level above 20 nM as positive, the test was positive in 67% of mesothelioma patients (95% confidence interval 60 to 74%), 11% of other-cancer patients and 0.4% (3 of 712) of patients without cancer. Among 936 samples that cytology did not report as cancer, 53 tested positive. Of these, 42 came from mesothelioma patients, 8 from other cancers and 3 from people with no cancer found. So 79% of these positives were mesothelioma and 94% were some cancer. The authors concluded that a positive result indicates likely cancer and supports further investigation. They added that the test is not sufficient alone, because 33% of mesothelioma cases were negative. They noted not every mesothelioma diagnosis rested on biopsy.

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: Retrospective diagnostic-accuracy study of consecutively collected pleural effusion samples; final diagnoses were established from pathology reports, hospital records and the Western Australian MM Registry
• Who was studied: 2156 pleural effusion samples from 1331 individuals (approximately 40% female) submitted to PathWest Laboratory Medicine, Western Australia, between 2005 and 2010 (a 67-month period). Final diagnoses were 183 malignant mesothelioma (MM), 436 non-MM malignancy (including 182 primary lung cancer) and 712 nonmalignant effusions.
• Exposure: Not an asbestos-exposure study. The test studied was soluble mesothelin in pleural effusion fluid, measured with the MESOMARK assay, with levels above 20 nM counted as elevated (positive). Results were not reported to the clinical team. Asbestos exposure was listed only for the 3 mesothelin-positive patients without malignancy (2 of 3 exposed).
• Main results:
  • Estimated median effusion mesothelin was 28 nM in MM patients, compared with 3.2 nM in patients with benign effusions and 4.7 nM in patients with non-MM malignancies (P less than 0.0001 for both comparisons), using the most recent sample per patient.
  • Using the most recent sample per individual (n = 1331) and the 20 nM cut-off, effusion mesothelin distinguished MM from all other causes of effusion with sensitivity 67% (95% CI, 60 to 74%) and specificity 95% (95% CI, 94 to 96%).
  • The area under the ROC curve for distinguishing MM patients (n = 183) from all other patients (n = 1148) was 0.877 (95% CI, 0.843 to 0.91).
  • 11% of effusions from patients with non-MM malignancies were mesothelin positive (50 of 436 per Table 1). Positivity rates were relatively higher, on small numbers, for ovarian cancer (5 of 11) and pancreatic cancer (3 of 10).
  • 3 of 712 (0.4%) effusions with mesothelin above 20 nM were not associated with malignancy.
  • Among 936 samples reported by cytology as nondiagnostic, nonmalignant, atypical or suspicious, 53 were mesothelin positive: 42 from MM patients, 8 from other malignancies and 3 with no evidence of malignancy. This gave a positive predictive value of 79% for MM and 94% for any malignancy.
  • Among 43 MM patients whose most recent effusion was reported by cytology as nondiagnostic or nonmalignant, mesothelin was elevated in 19. This included 17 of 36 (47%) samples taken before the diagnosis was made on a later biopsy or cytology sample.
  • Across all 271 effusion samples from the 183 MM patients, mesothelin was elevated in 170 (63%), including 8 of the 20 effusions from patients with sarcomatoid MM.
  • In 77 cases with an effusion sample taken before or within one week of a biopsy confirming MM, mesothelin was elevated in 51 (66%).
• The authors' conclusion: The authors concluded that a mesothelin-positive pleural effusion, whether or not malignant cells are seen, indicates the likely presence of malignancy and adds weight to further investigation to establish a malignant diagnosis.
• Limitations the authors state:
  • Because 33% of MM cases did not have an elevated mesothelin level, the authors stated the test is not sufficient as a stand-alone diagnostic test.
  • Not all MM cases were diagnosed by review of biopsy specimens.
  • Individuals contributed multiple samples with different reported pathologies at different times relative to diagnosis, which complicated the analysis.
  • Of the three 'false positive' cases, only one had a postmortem and one had relatively short follow-up.
  • The incidence of MM in this Western Australian setting is relatively high, and the authors acknowledged that pretest probability varies between centres.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Cytology, Pleural Effusion, Pathology.

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)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA — R. Filiberti, S. Parodi, et al. (2013)
• Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma — J. Creaney, I. van Bruggen, et al. (2007)
• Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology — J. Andrici, A. Sheen, et al. (2015)
• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)

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