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22904 Neuron-Specific Enolase (NSE)

Neuron-Specific Enolase (NSE)
Test Code: NSESO
Synonyms/Keywords
NSE Enolase
Useful For
A follow-up marker in patients with neuron-specific enolase-secreting tumors of any type
 
An auxiliary test in the diagnosis of small cell lung carcinoma
 
An auxiliary test in the diagnosis of carcinoids, islet cell tumors and neuroblastomas
 
An auxiliary tool in the assessment of comatose patients
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Serum​ ​Red Top Tube (RTT) ​Serum Separator Tube (SST) ​0.5 mL ​0.3 mL
Specimen Stability Information
Specimen Type Temperature Time
​Serum ​ ​Refrigerated (preferred) ​7 days
​Ambient ​7 days
Rejection Criteria
Hemolysis Gross
​Icterus Gross
Interference

All neuron-specific enolase (NSE) test results must be considered in the clinical context, and interferences or artifactual elevations should be suspected if the clinical NSE test results are at odds with the clinical picture or other tests. The laboratory should be contacted for assistance in these situations. 

Hemolysis can lead to significant artifactual NSE elevations, since erythrocytes contain NSE. 

Hemoglobin concentrations as low as 20 mg/dL were found to have an adverse effect on NSE testing.

Proton pump inhibitor treatment, hemolytic anemia, hepatic failure, and end stage renal failure can also result in artifactual NSE elevations.

Other false-positive results depend on the treating context. When performing NSE testing for tumor diagnosis or follow-up, epileptic seizure, brain injury, encephalitis, stroke, and rapidly progressive dementia might result in false-positive results. On the other hand, when NSE testing is performed to assist in neurological diagnosis, NSE-secreting tumors can represent a source of false-positive results.

NSE values can vary significantly between methods/assays. Serial follow-up should be performed with the same assay. If assays are changed, patients should have their baseline level reestablished. This assay is an immunometric assay and can, in rare situations, be affected by false low results in the presence of extremely high NSE concentrations ("hooking") or autoantibodies to NSE, as well as by false results in the presence of heterophile antibodies.

Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Clinic Laboratories Monday through Saturday​ 1 day​
Homogeneous Time-Resolved Fluorescence​
Reference Lab
Test Information

Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Enolase exists in the form of several tissue-specific isoenzymes, consisting of homo or heterodimers of 3 different monomer-isoforms (alpha, beta, and gamma). Neuron specific enolase (NSE) is a 78 kDa gamma-homodimer and represents the dominant enolase-isoenzyme found in neuronal and neuroendocrine tissues. Its levels in other tissues, except erythrocytes, are negligible. The biological half-life of NSE in body fluids is approximately 24 hours.

Due to this organ-specificity, concentrations of NSE in serum or, more commonly, cerebrospinal fluid (CSF), are often elevated in diseases that result in relative rapid (hours/days to weeks, rather than months to years) neuronal destruction. Measurement of NSE in serum or CSF can therefore assist in the differential diagnosis of a variety of neuron-destructive and neurodegenerative disorders. The most common application is in the differential diagnosis of dementias where elevated CSF concentrations support the diagnosis of rapidly progressive dementias, such as Creutzfeldt-Jacob Disease. NSE might also have utility as a prognostic marker in neuronal injury. For example, there is increasing evidence that elevated serum NSE levels correlate with a poor outcome in coma, particularly when caused by hypoxic insult.

NSE is also frequently overexpressed by neural crest-derived tumors. Up to 70% of patients with small cell lung carcinoma (SCLC) have elevated serum NSE concentrations at diagnosis, and approximately 90% of patients with advanced SCLC will have serum levels above the healthy reference range. Other neuroendocrine tumors with frequent expression of NSE include carcinoids (up to 66% of cases), islet cell tumors (typically <40% of cases), and neuroblastoma (exact frequency of NSE expression unknown). NSE levels in NSE-secreting neoplasms correlate with tumor mass and tumor metabolic activity. High levels have therefore some negative prognostic value. Falling or rising levels are often correlated with tumor shrinkage or recurrence, respectively.

Reference Range Information
< or =15 ng/mL
Serum markers are not specific for malignancy, and values may vary by method.
Interpretation

Serum neuron-specific enolase (NSE) measurement has its greatest utility in the follow-up of patients with tumors of any type that have been shown to secrete NSE. With successful treatment, serum concentrations should fall with a half-life of approximately 24 hours. Persistent NSE elevations in the absence of other possible causes (see Cautions) suggest persistent tumor. Rising levels indicate tumor spread or, in patients who had previously become NSE negative, recurrence.

In the context of a patient with a lung mass, disseminated malignancy of unknown origin or symptoms suggestive of paraneoplastic disease without identifiable tumor, elevated NSE suggests an underlying small cell lung carcinoma (SCLC).

In patients with suspected carcinoid, islet cell tumor, or neuroblastoma, who have no clear elevations in the primary tumor markers used to diagnose these conditions, an elevated serum NSE level supports the clinical suspicion.

-Carcinoid: chromogranin A, urinary 5-hydroxyindoleacetic acid, serum/blood 5-hydroxytryptamine

-Islet cell tumors: variety of peptide and amine-derived hormones, chromogranin A

-Neuroblastoma: vanillylmandelic acid and homovanillic acid

When considered alongside established outcome predictors of coma, such as Glasgow coma scale and other clinical predictors (papillary light responses, corneal reflexes, motor responses to pain, myoclonus, status epilepticus), electroencephalogram, sensory evoked potentials, measurement of serum NSE concentrations provides additional information. Elevated levels are indicative of a poor outcome. Currently, no established algorithms exist to combine serum NSE concentrations and the various other predictors into a composite score that gives clear predictive outcome information. The NSE measurement therefore needs to be considered in a qualitative or semi-quantitative fashion and carefully weighed against other predictors by a physician experienced in examining and managing coma patients.

Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​83520
Synonyms/Keywords
NSE Enolase
Ordering Applications
Ordering Application Description
​COM ​Neuron Specific Enolase
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Serum​ ​Red Top Tube (RTT) ​Serum Separator Tube (SST) ​0.5 mL ​0.3 mL
Specimen Stability Information
Specimen Type Temperature Time
​Serum ​ ​Refrigerated (preferred) ​7 days
​Ambient ​7 days
Rejection Criteria
Hemolysis Gross
​Icterus Gross
Interference

All neuron-specific enolase (NSE) test results must be considered in the clinical context, and interferences or artifactual elevations should be suspected if the clinical NSE test results are at odds with the clinical picture or other tests. The laboratory should be contacted for assistance in these situations. 

Hemolysis can lead to significant artifactual NSE elevations, since erythrocytes contain NSE. 

Hemoglobin concentrations as low as 20 mg/dL were found to have an adverse effect on NSE testing.

Proton pump inhibitor treatment, hemolytic anemia, hepatic failure, and end stage renal failure can also result in artifactual NSE elevations.

Other false-positive results depend on the treating context. When performing NSE testing for tumor diagnosis or follow-up, epileptic seizure, brain injury, encephalitis, stroke, and rapidly progressive dementia might result in false-positive results. On the other hand, when NSE testing is performed to assist in neurological diagnosis, NSE-secreting tumors can represent a source of false-positive results.

NSE values can vary significantly between methods/assays. Serial follow-up should be performed with the same assay. If assays are changed, patients should have their baseline level reestablished. This assay is an immunometric assay and can, in rare situations, be affected by false low results in the presence of extremely high NSE concentrations ("hooking") or autoantibodies to NSE, as well as by false results in the presence of heterophile antibodies.

Useful For
A follow-up marker in patients with neuron-specific enolase-secreting tumors of any type
 
An auxiliary test in the diagnosis of small cell lung carcinoma
 
An auxiliary test in the diagnosis of carcinoids, islet cell tumors and neuroblastomas
 
An auxiliary tool in the assessment of comatose patients
Reference Range Information
< or =15 ng/mL
Serum markers are not specific for malignancy, and values may vary by method.
Interpretation

Serum neuron-specific enolase (NSE) measurement has its greatest utility in the follow-up of patients with tumors of any type that have been shown to secrete NSE. With successful treatment, serum concentrations should fall with a half-life of approximately 24 hours. Persistent NSE elevations in the absence of other possible causes (see Cautions) suggest persistent tumor. Rising levels indicate tumor spread or, in patients who had previously become NSE negative, recurrence.

In the context of a patient with a lung mass, disseminated malignancy of unknown origin or symptoms suggestive of paraneoplastic disease without identifiable tumor, elevated NSE suggests an underlying small cell lung carcinoma (SCLC).

In patients with suspected carcinoid, islet cell tumor, or neuroblastoma, who have no clear elevations in the primary tumor markers used to diagnose these conditions, an elevated serum NSE level supports the clinical suspicion.

-Carcinoid: chromogranin A, urinary 5-hydroxyindoleacetic acid, serum/blood 5-hydroxytryptamine

-Islet cell tumors: variety of peptide and amine-derived hormones, chromogranin A

-Neuroblastoma: vanillylmandelic acid and homovanillic acid

When considered alongside established outcome predictors of coma, such as Glasgow coma scale and other clinical predictors (papillary light responses, corneal reflexes, motor responses to pain, myoclonus, status epilepticus), electroencephalogram, sensory evoked potentials, measurement of serum NSE concentrations provides additional information. Elevated levels are indicative of a poor outcome. Currently, no established algorithms exist to combine serum NSE concentrations and the various other predictors into a composite score that gives clear predictive outcome information. The NSE measurement therefore needs to be considered in a qualitative or semi-quantitative fashion and carefully weighed against other predictors by a physician experienced in examining and managing coma patients.

For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Clinic Laboratories Monday through Saturday​ 1 day​
Homogeneous Time-Resolved Fluorescence​
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​83520
For most current information refer to the Marshfield Laboratory online reference manual.