Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

Abstract

// Sylvia A.A.M. Genet 1 , 4 , Esther Visser 1 , 4 , Ben E.E.M. van den Borne 2 , Maggy Youssef-El Soud 3 , Huub N.A. Belderbos 5 , Gerben Stege 6 , Marleen E.A. de Saegher 7 , Federica Eduati 1 , 4 , Maarten A.C. Broeren 3 , 4 , Joost van Dongen 1 , 4 , Luc Brunsveld 1 , 4 , Daan van de Kerkhof 2 , 4 and Volkher Scharnhorst 1 , 2 , 4 1 Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands 2 Catharina Hospital Eindhoven, Eindhoven, The Netherlands 3 Máxima Medical Center, Eindhoven/Veldhoven, The Netherlands 4 Expert Center Clinical Chemistry Eindhoven, Eindhoven, The Netherlands 5 Amphia Hospital, Breda, The Netherlands 6 Sint Anna Hospital, Geldrop, The Netherlands 7 Sint Jans Gasthuis, Weert, The Netherlands Correspondence to: Daan van de Kerkhof, email: daan.vd.kerkhof@catharinaziekenhuis.nl Keywords: small-cell lung cancer; protein tumor markers; neuron-specific enolase; hemolysis correction equation Received: March 14, 2020     Accepted: June 15, 2020     Published: July 07, 2020 ABSTRACT Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis, prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics. Two serum pools were spiked with increasing amounts of hemolysate obtained from multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 μmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results. Therefore, a hemolysis correction equation should be used to correct falsely elevated NSE concentrations. Results of samples with an H-index above 30 μmol/L should not be reported to clinicians. Application of the equation illustrates the importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.