Pleural Fluid Mesothelin as an Adjunct to the Diagnosis of Pleural Malignant Mesothelioma

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.

Malignant pleural effusion: from bench to bedside

“…Mesothelin, first published as a useful biomarker in 2003, has however since been confirmed as a useful biomarker in serum in at multiple independent studies with very similar sensitivity and specificity levels, and its elevation in pleural fluid is also a useful guide to the presence of malignancy, including in initially cytology negative effusions [42,62,63].…”

Malignant Mesothelioma Biomarkers

“…In several studies on consecutive series of patients presenting with pleural effusions being investigated for malignancy by cytologic examination, it was shown that effusion mesothelin could be clinically useful. [15][16][17][18] In the context of an effusion being reported as being suspicious of malignancy, atypical, nonmalignant, or nondiagnostic, elevated mesothelin had a positive predictive value of > 57% (Table 1), which should prompt further clinical investigation of the patient rather than observation alone. Curiously, effusion mesothelin appears to have specificity for malignancy in general, rarely being positive in benign conditions.…”

Current best practice in the evaluation and management of malignant pleural effusions

“…Multiple serum and pleural biomarkers such as mesothelin, osteopontin and fibulin-3 have been investigated in MPE [Creaney et al 2014;Pass et al 2005Pass et al , 2012Porcel, 2013;Porcel et al 2004].…”