Test ID: NSE
Neuron-Specific Enolase (NSE), Serum
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
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
Method Name A short description of the method used to perform the test
Homogeneous Time-Resolved Fluorescence
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 0.5 mL
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild reject; Gross reject |
| Lipemia | Mild OK; Gross OK |
| Icterus | Mild reject; Gross reject |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Refrigerated (preferred) | 7 days |
| Ambient | 7 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 kD 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 which result in relative rapid (hours/days to weeks, rather than months to years) neuronal destruction. Measurement of NSE in serum of 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. There is, for example, increasing evidence that elevated serum NSE levels correlate with a poor outcome in coma, in particular 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 Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =15 ng/mL
Serum markers are not specific for malignancy, and values may vary by method.
Interpretation Provides information to assist in interpretation of the test results
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 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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-positives 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 be re-baselined. This assay is an immunometric assay, and can therefore 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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Burghuber OC, Worofka B, Schernthaner G, et al: Serum neuron-specific enolase is a useful tumor marker for small cell lung cancer. Cancer 1990;65:1386-1390
2. Lamberts SW, Hofland LJ, Nobels FR: Neuroendocrine tumor markers. Front Neuroendocrinol 2001;22:309-339
3. Aksamit AJ, Preissner CM, Homburger HA: Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt-Jacob disease. Neurology 2001;57:728-730
4. Riley RD, Heney D, Jones DR, et al: A systematic review of molecular and biological tumor markers in neuroblastoma. Clin Cancer Res 2004;10;4-12
5. Portela-Gomes GM, Hacker GW, Weitgasser R: Neuroendocrine cell markers for pancreatic islets and tumors. Appl Immunohistochem Mol Morphol 2004;12:183-192
6. Wijdicks EF, Hijdra A, Young GB, et al: Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review). Neurology 2006;67:203-210
Method Description Describes how the test is performed and provides a method-specific reference
Neuron specific enolase (NSE) is measured in this homogeneous automated immunofluorescent assay on the BRAHMS Kryptor. The Kryptor uses TRACE (Time Resolved Amplified Cryptate Emission) technology based on a non-radioactive transfer of energy. This transfer occurs between 2 fluorescent tracers: the donor (europium cryptate) and the acceptor (XL665). In the NSE assay, 2 monoclonal antibodies are labeled, 1 with europium cryptate and 1 with XL665. NSE is sandwiched between the 2 antibodies, bringing them into close proximity. When the antigen-antibody complex is excited with a nitrogen laser at 337 nm, some fluorescent energy is emitted at 620 nm and the rest is transferred to XL665. This energy is then emitted as fluorescence at 665 nm. A ratio of the energy emitted at 665 nm to that emitted at 620 nm (internal reference) is calculated for each sample. Signal intensity is proportional to the number of antigen-antibody complexes formed, and therefore to antigen concentration.
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Saturday; 2:30 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83520
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| NSE | Neuron Specific Enolase, S | 15060-7 |
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