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Abstract: Background: Blood-based markers for malignant mesothelioma (MM), particularly soluble mesothelin and osteopontin, are currently of great clinical interest. As there is some concern about the sensitivity of osteopontin in serum versus plasma, we compared them in the same patient population to mesothelin. Methods: Soluble mesothelin and osteopontin concentrations were determined by commercial assays in blood samples from 66 patients with pleural MM, 47 patients with non-malignant asbestos-related lung or pleural disease, 42 patients with other benign pleural and lung diseases and 21 patients with lung cancer. Results: Soluble mesothelin and osteopontin in serum and plasma were significantly elevated in MM patients compared to patients with benign lung and pleural disease. At a level of specificity of 95% relative to patients with benign disease, the sensitivity of mesothelin in serum and plasma at presentation with symptoms was 67%, and for osteopontin in the plasma was 40% and in the serum was 20% for MM patients. Combining the serum mesothelin and plasma osteopontin markers using a logistic regression model did not significantly increase the area under the receiver operator curve. Conclusion: Plasma osteopontin has a superior diagnostic accuracy to serum. As the choice of blood sample type has limit effect on soluble mesothelin sensitivity, plasma should be collected for biomarker evaluation in patients suspected of having mesothelioma. [Copyright &y& Elsevier]

Background: The diagnosis of malignant mesothelioma is frequently difficult, the most common differential diagnosis being reactive pleural conditions and metastatic adenocarcinoma. Soluble mesothelin levels in serum have recently been shown to be highly specific and moderately sensitive for mesothelioma. As most patients with mesothelioma present with exudative effusions of either the pleura or the peritoneum, a study was undertaken to determine if levels of mesothelin were raised in these fluids and if the increased levels could help to distinguish mesothelioma from other causes of exudative effusion. Methods: Pleural fluid was collected from 192 patients who presented to respiratory clinics (52 with malignant mesothelioma, 56 with non-mesotheliomatous malignancies and 84 with effusions of non-neoplastic origin). Peritoneal fluid was collected from 42 patients (7 with mesothelioma, 14 with non-mesotheliomatous malignancies and 21 with benign effusions). Mesothelin levels were determined in effusion and serum samples by ELISA. Results: Significantly higher levels of mesothelin were found in effusions of patients with mesothelioma; with a specificity of 98%, the assay had a sensitivity of 67% comparing patients with mesothelioma and those with effusions of non-neoplastic origin. In 7 out of 10 cases mesothelin levels were raised in the effusion collected 3 weeks to 10 months before the diagnosis of mesothelioma was made; in 4 out of 8 of these, mesothelin levels were increased in the effusion but not in the serum. Conclusions: Measurement of mesothelin concentrations in the pleural and/or peritoneal effusion of patients may aid in the differential diagnosis of mesothelioma in patients presenting with effusions. [ABSTRACT FROM AUTHOR]

Patients with Malignant Mesothelioma (MM) develop unidentified auto-antibodies to MM tumour antigens. This study was conducted to identify the targets of MM patient auto-antibodies in order to try to understand more of the anti-tumour response and to determine if these antibodies might be helpful for diagnosis or prognostication. Using MM patient sera in a Western immunoblott screening strategy, no common immunoreactive proteins were identified. The sera from one longterm survivor recognised a protein band of 50-60 kDa present in cell lysates from four of five MM cell lines tested. The immunoreactive proteins in this band were identified by 2D electrophoretic separation of a MM cell line protein lysate, followed by analysis of excised immunoreactive proteins on a MALDI TOF mass spectrometer and peptide mass fingerprinting. The immunoreactive proteins identified were vimentin (accession gi55977767) and the ATP synthase (F1- ATPase) beta chain (accession gi114549 and gi47606749). ELISA assays were developed for antibodies to these proteins. Neither vimentin (median and 95% CI 0.346; 0.32-0.468 for MM patients, 0.327; 0.308-0.428 for controls) nor ß-F1-ATPase (0.257; 0.221-0.453 for MM patients, 0.263; 0.22-0.35 for controls) showed significant differences in autoantibody levels between a group of MM patients and controls. Using a dichotomized antibody level (high, low) for these targets we demonstrated that vimentin antibody levels were not associated with survival. In contrast, high ß-F1-ATPase antibody levels were significantly associated with increased median survival (18 months) compared to low ß F1 ATPase antibody levels (9 months; p = 0.049). Immunohistochemical analysis on a MM tissue microarray showed cytoplasmic staining in 28 of 33 samples for vimentin and strong cytoplasmic staining in14 and weak in 16 samples for ß-F1-ATPase. Therefore antibodies to neither vimentin nor ß-F1-ATPase are useful for differential diagnosis of MM, however high antibody levels to ß-F1-ATPase may be associated with increased survival and this warrants further investigation. [ABSTRACT FROM AUTHOR]