Neuron-specific Enolase (NSE)

Neuron-specific enolase (NSE) is an enzyme that is found in the cytoplasm of neurons and neuroendocrine cells.^2,3 The production of NSE occurs late in neural differentiation, thus making NSE an index of neural maturation.² Increased serum levels of NSE may occur in patients with of neuroendocrine tumors (NETs).^2,4-13 A number of NETs are considered to be “nonfunctioning” in that they do not produce elevated serum concentrations of substances that cause endocrine symptoms. NSE is similar to chromogranin A (CgA) in that it can serve as a general neuroendocrine tumor marker that can be of clinical value in in the assessment of non-functioning tumors.^4,14 NSE can be particularly useful in the assessment of patients with high-grade, poorly differentiated tumors.^4,14

Serum NSE levels are often elevated in patients with small-cell lung cancer (SCLC) and NSE levels are applied as a biomarker for disease staging and monitoring.^3,11,13-27 NSE levels have been shown to correlate with tumor burden, number of metastatic sites and response to treatment in SCLC.^6,28,29 A meta-analysis of 11 studies determined that SCLC patients with higher levels of NSE had a poorer prognosis than those with lower levels of NSE.³⁰

Increased levels of NSE have been also reported in non-small cell lung cancer (NSCLC).^2,31,32 Differentiation between SCLC and NSCLC can have prognostic and therapeutic value, due to the dissimilar behavior of these malignancies.^2,33 In a comparative analysis of the performance of several NSE assays, Stern and coworkers found that the Brahms Kryptor assay had a 22% sensitivityfor distinguishing cancer patients (SCLC and NSCLS) from benign lung disease with a specificity of 95% using a cut-off concentration of 20 ug/L.³⁴ In the same study, the Brahms assay had a 55% sensitivity for distinguishing SCLC form NSCLS at 95% specificity,³⁴ employing an NSE cut-off of 21ug/L. This was the highest sensitivity of the seven NSE methods evaluated.

Raised serum levels of NSE have been found in patients with neuroblastoma, especially in widespread and metastatic disease, with high serum levels correlated with significantly worse outcome in terms of disease-free survival.^35-37 Increased serum NSE levels have also been observed in patients with diverse conditions including: melanoma, seminoma, renal cell carcinoma, Merkel cell tumor, carcinoid tumors, dysgerminomas and immature teratomas, malignant pheochromocytoma, Guillain-Barrésyndrome and Creutzfeldt-Jakob disease.²

Measurement of serum NSE has been applied to the assessment of neuronal injury³⁷ and the estimation of brain damage in conditions including: ischemic stroke,³⁸ intracerebral hemorrhage,^39,40 seizure,⁴¹ after cardiopulmonary resuscitation for cardiac arrest⁴² and in traumatic brain injury.⁴³