Hemolysis correction factor in the measurement of serum neuron-specific enolase

Abstract

Neuron-specific enolase (NSE) is comprised of two isoforms, ag and gg, of the glycolytic enzyme enolase. It is present almost exclusively in neurons and neuroendocrine tissues (1–3). The protein is a valuable tumor marker for monitoring the outcome and disease course in patients with cancer of the neuroendocrine type, in particular small cell lung cancer and neuroblastoma (4, 5). In addition, the concentration of NSE in biological fluids might be a useful parameter for the assessment of neural brain damage as NSE was shown to be released into cerebrospinal fluid and blood following cerebral injury (5, 6). However, the ag-isoform was also reported to be present in circulating blood cells, especially in erythrocytes and platelets (3, 7). As a consequence, slight hemolysis – even undetectable to the naked eye (3) – can produce falsely increased degrees of immunoreactivity (1). Considering the role of NSE as an important biomarker, interpretation of NSE results is unreliable unless accompanied by an estimate of red cell disruption (3). In the case of hemolysis, it is common practice to include a comment on the laboratory report and not give the NSE value itself. We examined the possibility of using data correction to report a clinically more reliable result when measuring NSE in hemolysed serum, instead of reporting a comment that the assay could not be performed. NSE was measured using a sandwich immunoassay with the electrochemiluminescence (ECL) technology installed on a Modular E170 (Roche Diagnostics, Mannheim, Germany). Evaluation of the magnitude of hemolysis was achieved using the hemolytic index (H). The serum index was routinely measured with a Cobas 6000 analyzer (Roche Diagnostics, Mannheim, Germany) using absorbance values of two bichromatic readings (570 and 600 nm, and 660 and 700 nm). The absorbance values are converted into semi-