Determination of HE4 in pleural fluid and ratio : considerations and diagnostic performance for malignant pleural effusion

Objectives: The objectives of this study included assessing the diagnostic performance of HE4 in malignant pleural effusions (MPEs) and identifying the benign etiologies associated with higher HE4 concentrations. Methods: The study involved patients with pleural effusion (PE) treated at Part Taulí University Hospital. PE and serum samples were collected and analyzed. Diagnosis of MPE was established by the presence of a positive cytology and/or positive pleural biopsy. HE4 concentrations in LP and serum - among other parameters - were measured on an ECLIA-Cobas e801 (Roche Diagnostics) analyzer. Subsequently, pleural fluid to serum HE4 ratio (PF/serum HE4 ratio) was calculated. Patients were assigned to different groups according to final diagnosis, transudate vs. exudate, MPE etiology and estimated glomerular filtration rate (eGFR). An evaluation was performed of the diagnostic performance of HE4 for MPE. Results: A total of 253 PF and serum samples were included. In patients with benign pleural effusion (BPE), transudates contained higher levels of HE4, as compared to exudates. The highest PF-HE4 concentrations and ratios were observed in MPEs, especially in patients with non-small cell lung cancer + ovarian cancer. The cut-off values established showed a sensitivity of 16.7% (PF-HE4) and 12.1% (ratio), with a 100% specificity, respectively. Following cut-off adjustment, higher sensitivity values were observed in patients with an eGFR ≥ 30 mL/min/1.73m 2. Conclusions: Elevated HE4 concentrations may support MPE diagnosis and predict histology. Transudates contain elevated levels of HE4 and lower PF/serum-HE4 ratios. In the investigation of solid neoplasms, different serum HE4 cut-off values should be used for patients with PE, heart failure, cirrhosis or renal insufficiency.