Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma

Background

Malignant mesothelioma (MM), a primarily asbestos-induced tumour, has a poor prognosis, with over-all 5-year survival less than 5%. Tumour biomarkers are being intensely investigated in MM as aids to diagnosis and prognosis. Hyaluronic acid (HA) is produced in MM but its role in prognostication remains uncertain.

Materials and methods

HA concentrations were determined in matching serum and pleural effusion of 96 MM patients, 26 lung cancer patients and 42 patients with benign effusions resulting from infectious, cardiac, renal, liver and rheumatoid diseases and compared to the current ‘best practice’ biomarker, mesothelin. Liver and kidney function were determined for each patient. Diagnostic accuracy was determined by area under the receiver operator characteristic curve (AUC) analysis following logistic regression modelling. Difference in survival between groups was determined by both log-rank test and Cox proportional hazards regression modelling.

Results

For effusion HA, the AUC (IQ range) was 0.89 (0.82–0.94) and for effusion mesothelin, it was 0.85 (0.78–0.90). Serum HA was not diagnostically useful. A combined measure of effusion HA, and serum and effusion mesothelin had an AUC of 0.92 (0.86–0.96), which was significantly higher than effusion mesothelin alone. Effusion HA had a biphasic distribution in MM patients, dichotomised at a concentration of 75 mg/L. The median survival of MM patients with high effusion HA was 18.0 (13.7–22.4) months, significantly longer than those with low HA effusion levels (12.6 months (8.4–16.8), p = 0.004). Serum HA, and effusion and serum mesothelin were not significant prognostic indicators.

Conclusion

This study demonstrates that a combined biomarker panel has greater diagnostic accuracy than effusion mesothelin alone, and that significant prognostic information is provided by effusion HA.