The diagnostic accuracy of HE4 in the differential diagnosis of pleural effusions

Abstract

Background: Pleural effusions are challenging to diagnose, with approximately 20-50% of malignant effusions not diagnosed by cytology. Human epididymal protein 4 (HE4) may be useful in the differential diagnosis of pleural effusions. In serum, this biomarker shows false-positive results in some benign diseases. The aim of this study was to evaluate the diagnostic utility of HE4 in this setting and to identify false positives.

Methods: Concentrations of HE4, adenosine deaminase, % polynuclear cells, and C-reactive protein, were determined in 238 pleural fluid samples and the estimated glomerular filtration rate (eGFr) in serum.

Results: HE4 values ​​differed significantly (p < 0.01) between malignant [median (IQR)] [1065 (2085)] pmol/L and benign effusions [699 (589)] pmol/L. HE4 concentrations in gynecological and pulmonary tumors were significantly higher than in other tumors. For a cut-off point of 3050 pmol/L, 22 % sensitivity and 100 % specificity were obtained. In patients with benign disease, significant increases in HE4 were identified only in those with eGFr < 30 mL/min/1.73 m2 [1050(596)] pmol/L, and not in those with eGFr > 30 mL/min/1.73 m2 [597(532)] pmol/L). Two cut-offs were established for maximum specificity, depending on the eGFr: 3050 pmol/L for eGFr < 30 mL/min/1.73 m2 and 1992 pmol/L for eGFr > 30 mL/min/1.73 m2. A sensitivity of 28.5 % was obtained for patients with eGFr > 30 mL/min/1.73 m2 and 36.3 % for patients with eGFr < 30 mL/min/1.73 m2. The sensitivity using a specific cut-off point was 29.7 %.

Conclusions: The determination of HE4 in pleural fluids demonstrates high specificity and low sensitivity. The use of specific cutoff points that are clinically adjusted improves sensitivity while maintaining maximum specificity.