Clinical Significance of Serum Mesothelin in Patients with Mesothelioma and Lung Cancer

Abstract

Purpose: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC).To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled. Experimental Design: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker. Results: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM. Conclusions: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM.We found that serum SMRP dosage may prove helpful in LC diagnosis as well.These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.

Clinical utility of diagnostic markers for malignant pleural mesothelioma

“…We also showed that there is a relationship between serum mesothelin level at diagnosis and patients survival [70]. Similar results were also published by Cristaudo et al [72], but other authors did not find such relationship [74].…”

“…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.…”

Serum mesothelin and other biomarkers: what have we learned in the last decade?

“…Our data, in particular, provide the evidence that high SMRP dosage can be considered as an independent prognostic tool for patients with epithelioid MPM and suggest that this dosage could be useful both as a screening test for diagnosis (11), interpreted, of course, taking into account the other information available to the clinical context.…”

“…Other studies (8)(9)(10)(11)(12)(13)(14) confirmed that serum SMRP was a promising marker for diagnosis, prognosis and clinical monitoring of MPM. High SMRP concentrations were detected in all the studies only in the epithelioid and mixed MPM.…”

Asbestos-Related Research: First Objectivity then Conclusions

“…No marker discriminates well between Mt and other cancers [19,24], which, in conjunction with uncertainty about progenitor cells [14], makes the demarcation of Mt as an entity indistinct. Mesothelin and osteopontin have been considered promising markers, but both have limitations [18,25,26]. Although several studies indicated that mesothelin is useful for screening, other evidence indicates that this marker has a considerable false-positivity rate [27], being insufficiently sensitive for early diagnostics [28].…”