The Use of Pleural Fluid sCD44v6/std Ratio for Distinguishing Mesothelioma from Other Pleural Malignancies

Abstract

Differentiating metastatic adenocarcinoma from malignant pleural mesothelioma is often a challenging task. Spliced forms of CD44, such as exon v6 (CD44v6), have been implicated in tumor metastasis. We examined the diagnostic performance of soluble (s) CD44v6 and CD44 standard (sCD44std) as biomarkers for nonmesothelioma pleural malignancies in a retrospective series. The pleural fluid from 161 patients with pleural effusion (33 mesotheliomas, 104 nonmesothelioma malignancies, and 24 benign conditions) was analyzed for sCD44v6 and sCD44std levels using an enzyme-linked immunosorbent assay kit. The ability of sCD44v6 and sCD44std levels and the sCD44v6/std ratio for distinguishing mesothelioma from nonmesothelioma malignancy were examined. Median pleural fluid concentrations of sCD44v6 but not sCD44std were significantly higher in patients with nonmesothelioma malignancy (101.5 ng/mL) than in those with mesothelioma (38 ng/mL, p < 0.0001). Fluids from metastatic squamous cell carcinomas exhibited particularly high sCD44v6 levels (388 ng/mL). A cutoff value of 100 ng/mL had the highest accuracy for distinguishing mesothelioma from nonmesothelioma malignancy (sensitivity 53% and specificity 88%) or metastatic adenocarcinoma (sensitivity 60% and specificity 88%). An sCD44v6/std ratio of more than 0.34 discriminated between adenocarcinoma and mesothelioma with a sensitivity of 60%, a specificity of 93%, a likelihood ratio positive of 9.97, and an area under the curve of 0.87 (95% confidence interval: 0.80-0.94). The pleural fluid sCD44v6/std ratio may be a new diagnostic marker in the differential diagnosis between primary mesothelioma and other pleural malignancies. Values greater than 0.34 predict nonmesothelioma malignancy and may be a help in determining whether an invasive thoracoscopy is necessary.