Utility of human epididymis protein 4 in the differential diagnosis of ascites

Authors: Silvia Bérgamo , Jaume Trapé , Laura González García , Carolina González Fernández , Carme Vergara , Noelia de la Torre , Glòria Trujillo , Dolors Estivill , Marco Antonio Álvarez González , Laia Bosch , Marta Otero Viñas , Carmen Bergós , Silvia Catot , Domingo Ruiz Hidalgo , Sandra Ros , Francesc Sant

Abstract

Background and aims: Human epididymal protein 4 (HE4) may be a useful tool in the differential diagnosis of malignant ascites. The aim of this study was to evaluate the diagnostic utility of HE4 for detecting malignant ascites, taking into account the possible false positives identified with adenosine deaminase (ADA), C-reactive protein (CRP), % polynuclear cells (%PMN) and glomerular filtration rate (eGFR).

Methods: Concentrations of HE4, ADA, %PMN and CRP were determined in 114 samples of peritoneal fluid and creatinine in serum in order to calculate eGFR.

Results: Concentrations of HE4 presented significant differences (P = 0.028) in benign [median (interquartile range)] [582(372)] pmol/L) and malignant ascites ([8241(367)] pmol/L. Sensitivity was 21.2% and specificity 100%. Significant differences were also observed for HE4 between tumors of gynecological origin ([3165(8769)] pmol/L) and others ([665(663)] pmol/L), with a sensitivity of 67% and a specificity of 100%. Classifying according to possible false positives (ADA > 45U/L, CRP > 50 mg/L, %PMN > 90 and eGFR < 30 mL/min/1.73 m2) at maximum specificity, a sensitivity of 33.3% was obtained for HE4, with a cut-off point of 2660 pmol/L. Without possible false positives (ADA < 45U/L, CRP < 50 mg/L, %PMN < 90 and eGFR ≥ 30 mL/min/1.73 m2), a sensitivity of 37.7% was obtained at 100% specificity for a cut-off point of 1041 pmol/L. Applying these criteria to the entire group, a sensitivity of 36.4% was obtained at maximum specificity.

Conclusions: HE4 allows the identification of malignant ascites with moderate sensitivity at maximum specificity. HE4 levels can differentiate between tumors of gynecological origin and others. Classification according to possible false positives increases sensitivity without losing specificity.

Keywords: ADA; CRP; Differential diagnostic; False positives; HE4; Malignant ascites.