Utility of Osteopontin and Serum Mesothelin in Malignant Pleural Mesothelioma Diagnosis and Prognosis Assessment

Abstract

Purpose: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment.We compared diagnostic and prognostic values of mesothelin and osteopontin in172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects. Experimental Design: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestosexposed healthy subjects. Results were correlated with patient's diagnosis and survival. Results: Serum osteopontin level was higher in MPM patients compared with healthy asbestosexposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients. Conclusions: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.

Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells

“…Moreover, the acquisition of chemoresistance by HA-CD44 interaction could be advantage for MPM cells to protect themselves by anti-cancer agents. These ideas are supported by previous reports which demonstrated MPM to be associated with elevated levels of OPN and HA in the pleural effusion (Thylen et al, 1997;Pass et al, 2005;Grigoriu et al, 2007).…”

“…For instance, it has been reported that small cell lung cancer cells, myeloma cells, glioma cells and colon cancer cells were protected from apoptosis induced by various anticancer agents when the cells were plated on ECM (Damiano et al, 1999;Sethi et al, 1999;Uhm et al, 1999;Kouniavsky et al, 2002). MPM cells are surrounded by pleural effusion, which contains a variety of ECM including hyaluronate (HA) and osteopontin (OPN) (Thylen et al, 1997;Pass et al, 2005;Grigoriu et al, 2007). The ability to grow in pleural fluid suggests that the MPM cells are capable of surviving and proliferating against apoptosis under the influence of this particular microenvironment.…”

“…OPN has been associated with cancer progression, metastasis and apoptosis (Rangaswami et al, 2006). Several studies have revealed elevated levels of OPN in serum and pleural effusion to be observed in patients with MPM (Pass et al, 2005;Grigoriu et al, 2007), thus suggesting the involvement of OPN in the pathogenesis of MPM. In fact, OPN was recently demonstrated to mediate MPM cell proliferation and migration (Ohashi et al, 2009).…”

Clinical utility of diagnostic markers for malignant pleural mesothelioma

“…Surgery resulted in a sharp decrease in serum mesothelin while chemotherapy induced no change [67]. A significantly larger series from France confirmed the diagnostic utility of mesothelin [69,70] followed by similar results in series from Italy [71,72] and Netherlands [24]. Globally analysed, the results from these different teams showed that serum mesothelin is a good diagnostic marker with areas under ROC curved around 0.8-0.85.…”

“…However up to one third of mesotheliomas do not have elevated levels of mesothelin with a minimum cut-off at 1 nmol/l and up to 40-50% of MPM may be considered negative if a specificity of at least 95% is requested. Moreover about 20% of lung adenocarcinomas have elevated levels of serum mesothelin [24,70].…”