Pleural Fluid Mesothelin May Help Diagnose Mesothelioma

Laurie Barclay, MD

August 31, 2009

August 31, 2009 — Pleural fluid mesothelin is a helpful adjunct to cytology examination in patients with an undiagnosed pleural effusion, according to the results of a study reported in the September 1 issue of the American Journal of Respiratory and Critical Care Medicine.

"Pleural effusion, or the accumulation of fluid in the pleural cavity, can be maddeningly difficult to diagnose as a wide variety of malignant and benign causes exist," lead author Helen Davies, MRCP, from the Oxford Centre for Respiratory Medicine and Oxford University, United Kingdom, said in a news release. "One of the causes, malignant pleural mesothelioma, is a relatively rare cancer, but its incidence is rapidly increasing on a global scale."

The goal of this study was to evaluate the diagnostic role of pleural fluid mesothelin in identifying malignant mesothelioma in a total of 209 patients with undiagnosed pleural effusion, as well as the effect of common clinical factors that could affect measurement accuracy.

The investigators prospectively collected fluid from 167 patients presenting with pleural effusions. They also measured mesothelin levels in serial pleural fluid samples from 33 patients who underwent repeated drainage and in 32 patients before and after pleurodesis. Using enzyme-linked immunosorbent assay, they quantified mesothelin levels in a total of 424 pleural fluid and 64 serum samples.

In patients with mesothelioma (n = 24), pleural fluid mesothelin concentrations were significantly higher vs those with metastatic carcinomas (n = 67) and benign effusions (n = 75). Median mesothelin concentrations and interquartile range (IQR; from the 25th to the 75th percentile) were 40.3 nM (IQR, 18.3 - 68.1 nM), 6.1 nM (IQR, 1.5 - 13.2 nM), and 3.7 nM (IQR, 0.0 - 12.4 nM), respectively (P < .0001).

In the diagnosis and exclusion of mesothelioma, mesothelin measurement was superior to cytologic examination (sensitivity, 71% vs 35%; specificity, 89% vs 100%; negative predictive value [NPV], 95% vs 82%, respectively). For patients who had "suspicious" cytologic features, pleural fluid mesothelin was 100% specific for mesothelioma. The NPV of mesothelin was 94% for 105 effusions in which cytologic examination results were negative.

"This study suggests a way for clinicians to more readily identify these cases from the start," Dr. Davies said. "Because mesothelioma has a median survival time of 12 months, minimizing the number of invasive procedures and tests patients require is crucial to reduce morbidity and the time they need to spend in hospital. An earlier diagnosis also allows speedier interventions to relieve symptoms as well as initiation of other treatments such as chemotherapy or radiotherapy if appropriate."

Pleural fluid mesothelin levels had excellent intraindividual reproducibility, with mean variation of –0.15 ± 8.41 nM in samples collected within 7 days from patients with mesothelioma. Reliability of mesothelin level measurements remained stable even after pleurodesis or in the presence of bacteria.

"Pleural fluid mesothelin provides a valuable adjunct in the diagnostic assessment of patients presenting with pleural effusions, especially when cytological examination is not definitive, and can improve clinical practice," Dr. Davies concluded. "Claims for worker's compensation may also be instigated once the diagnosis is confirmed."

Limitations of this study include a small number of cases with "suspicious" pleural fluid cytologic features ultimately diagnosed as underlying mesothelioma, and a high proportion of mesothelioma cases requiring validation in settings of low mesothelioma incidence.

The British Lung Foundation, the Fondo de Investigacion Sanitaria, a Department of Health Clinical Senior Lecturer Award, the Medical Research Council, the NIHR Oxford Biomedical Research Centre, a Medical Research Council Project Grant, and a Department of Health Clinical Senior Lecturer Award supported this study.

Am J Respir Crit Care Med. 2009;180:437-444. Abstract

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