Neuron-specific Enolase (NSE)

CPT: 86316
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Special Instructions

Values obtained with different assay methods should not be used interchangeably in serial testing. It is recommended that only one assay method be used consistently to monitor each patient's course of therapy. This procedure does not provide serial monitoring; it is intended for one-time use only. If serial monitoring is required, please use the serial monitoring number 480137 to order.

Expected Turnaround Time

3 - 10 days

Related Information

Related Documents

Specimen Requirements




0.5 mL

Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)


Red-top tube or gel-barrier tube


Transfer separated serum to a plastic transport tube as quickly as possible after the clot has formed (within 30 minutes of collection).

Storage Instructions


Stability Requirements



Room temperature

7 days


7 days


14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Hemolysis; gross icterus; plasma specimen

Test Details


An aid in the detection and monitoring of neuroendocrine tumors (NETs), particularly those associated with small-cell lung cancer (SCLC)


This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Because erythrocytes a contain large amount of NSE, hemolysis can cause falsely elevated levels.1


The ThermoFisher/BRAHMS KRYPTOR® assay employs Time-Resolved Amplified Cryptate Emission (TRACE) technology based on a non-radioactive energy transfer between a donor (europium cryptate) and an acceptor (XL665) in a sandwich immunofluorescent format using two mouse monoclonal antibodies.

Reference Interval

0.0−17.6 ng/mL

Additional Information

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


1. Ramont L, Thoannes H, Volondat A, Chastang F, Millet MC, Marquart MF. Effects of hemolysis and storage condition on neuron-specific enolase (NSE) in cerebrospinal fluid and serum: implications in clinical practice. Clin Chem Lab Med. 2005;43(11):1215-1217.
2. Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125-143.26530364
3. Hofland J, Zandee WT, de Herder WW. Role of biomarker tests for diagnosis of neuroendocrine tumors. Nat Rev Endocrinol. 2018 Nov;14(11):656-669.30158549
4. Oberg K, Jelic S; ESMO Guidelines Working Group. Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up. Ann Oncol. 2009 May;20 Suppl 4:150-153.19454440
5. Korse CM, Taal BG, Vincent A, et al. Choice of tumour markers in patients with neuroendocrine tumors is dependent on the histological grade. A marker study of Chromogranin A, Neuron specific enolase, Progastrin-releasing peptide and cytokeratin fragments. Eur J Cancer. 2012 Mar;48(5):662-671.21945100
6. Yao JC, Pavel M, Phan AT, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 2011 Dec;96(12):3741-3749.21994954
7. O'Toole D, Grossman A, Gross D, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology. 2009;90(2):194-202.19713711
8. de Herder WW. Biochemistry of neuroendocrine tumors. Best Pract Res Clin Endocrinol Metab. 2007 Mar;21(1):33-41.17382264
9. Eriksson B, Oberg K, Stridsberg M. Tumor markers in neuroendocrine tumors. Digestion. 2000;62 Suppl 1:33-38.10940685
10. Bajetta E, Ferrari L, Martinetti A, et al. Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer. 1999 Sep 1;86(5):858-865.10463986
11. Baudin E, Gigliotti A, Ducreux M, et al. Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumors. Br J Cancer. 1998 Oct;78(8):1102-1107.9792158
12. Jiang SX, Kameya T, Shoji M, Dobashi Y, Shinada J, Yoshimura H. Large cell neuroendocrine carcinoma of the lung: a histologic and immunohistochemical study of 22 cases. Am J Surg Pathol. 1998 May;22(5):526-537.9591721
13. Nobels FR, Kwekkeboom DJ, Coopmans W, et al. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab. 1997 Aug;82(8):2622-2628.9253344
14. Oberg K, Couvelard A, Delle Fave G, et al. ENETS Consensus Guidelines for Standard of Care in Neuroendocrine Tumours: Biochemical Markers. Neuroendocrinology. 2017;105(3):201-211.28391265
15. Petrović M, Bukumirić Z, Zdravković V, Mitrović S, Atkinson HD, Jurišić V. The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer. Med Oncol. 2014 Feb;31(2):823.24375395
16. Kanakis G, Kaltsas G. Biochemical markers for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Best Pract Res Clin Gastroenterol. 2012 Dec;26(6):791-802.23582919
17. Franjević A, Pavićević R, Bubanović G. Differences in initial NSE levels in malignant and benign diseases of the thoracic wall. Clin Lab. 2012;58(3-4):245-252.22582497
18. Kulpa J, Wójcik E, Reinfuss M, Kołodziejski L. Carcinoembryonic antigen, squamous cell carcinoma antigen, CYFRA 21-1, and neuron-specific enolase in squamous cell lung cancer patients. Clin Chem. 2002 Nov;48(11):1931-1937.12406978
19. Giovanella L, Ceriani L, Bandera M, Garancini S. Immunoradiometric assay of chromogranin A in the diagnosis of small cell lung cancer: comparative evaluation with neuron-specific enolase. Int J Biol Markers. Jan-Mar 2001;16(1):50-55.11288956
20. Quoix E, Purohit A, Faller-Beau M, Moreau L, Oster JP, Pauli G. Comparative prognostic value of lactate dehydrogenase and neuron-specific enolase in small-cell lung cancer patients treated with platinum-based chemotherapy. Lung Cancer. 2000 Nov;30(2):127-134.11086206
21. Fizazi K, Cojean I, Pignon JP, et al. Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma. Cancer. 1998 Mar 15;82(6):1049-1055.9506348
22. Jørgensen LG, Osterlind K, Genollá J, et al. Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres. Br J Cancer. 1996 Aug;74(3):463-467.8695366
23. Giovanella L, Ceriani L, Bandera M, Beghe B, Roncari G. Evaluation of the serum markers CEA, NSE, TPS and CYFRA 21.1 in lung cancer. Int J Biol Markers. Jul-Sep 1995;10(3):156-160.8551058
24. Spinazzi A, Soresi E, Borghini U, Boffi R, Vigorelli R, Scoccia S. Clinical value of neuron specific enolase and tissue polipeptidic antigen for the management of patients with lung cancer. J Nucl Med Allied Sci. Oct-Dec 1990;34(4 Suppl):141-145.1965446
25. Harding M, McAllister J, Hulks G, et al. Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance? Br J Cancer. 1990 Apr;61(4):605-607.2158809
26. Gronowitz JS, Bergström R, Nôu E, et al. Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. Cancer. 1990 Aug 15;66(4):722-732.2167141
27. Cooper EH, Splinter TA, Brown DA, Muers MF, Peake MD, Pearson SL. Evaluation of a radioimmunoassay for neuron specific enolase in small cell lung cancer. Br J Cancer. 1985 Sep;52(3):333-338.2994704
28. Strosberg JR, Halfdanarson TR, Bellizzi AM, et al. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas. 2017 Jul;46(6):707-714.28609356
29. Yao JC, Lombard-Bohas C, Baudin E, et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010 Jan 1;28(1):69-7619933912
30. Zhao WX, Luo JF. Serum neuron-specific enolase levels were associated with the prognosis of small cell lung cancer: a meta-analysis. Tumour Biol. 2013 Oct;34(5):3245-3248.23775010
31. Molina R, Auge JM, Filella X, et al. Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer. Anticancer Res. May-June 2005;25(3A):1773-1778.16033098
32. Giovanella L, Piantanida R, Ceriani, L et al. Immunoassay of neuron-specific enolase (NSE) and serum fragments of cytokeratin 19 (CYFRA 21.1) as tumor markers in small cell lung cancer: clinical evaluation and biological hypothesis. Int J Biol Markers. Jan-Mar 1997;12(1):22-26.9176714
33. Paone G, De Angelis G, Munno R, et al. Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1. Eur Respir J. 1995 Jul;8(7):1136-1140.7589398
34. Stern P, Bartos V, Uhrova J, et al. Performance characteristics of seven neuron-specific enolase assays. Tumour Biol. 2007;28(2):84-92.17259755
35. Riley RD, Heney D, Jones DR, et al. A systematic review of molecular and biological tumor markers in neuroblastoma. Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):4-12.14734444
36. Zeltzer PM, Marangos PJ, Evans AE, Schneider SL. Serum neuron-specific enolase in children with neuroblastoma. Relationship to stage and disease course. Cancer. 1986 Mar 15;57(6):1230-1234.3002599
37. Stammet P, Collignon O, Hassager C, et al. Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C. J Am Coll Cardiol. 2015 May 19;65(19):2104-2114.25975474
38. Anand N, Stead LG. Neuron-specific enolase as a marker for acute ischemic stroke: a systematic review. Cerebrovasc Dis. 2005;20(4):213-219.16123539
39. Wolf H, Frantal S, Pajenda GS, et al. Predictive value of neuromarkers supported by a set of clinical criteria in patients with mild traumatic brain injury: S100B protein and neuron-specific enolase on trial: clinical article. J Neurosurg. 2013 Jun;118(6):1298-1303.23451906
40. Brea D, Sobrino T, Blanco M, et al. Temporal profile and clinical significance of serum neuron-specific enolase and S100 in ischemic and hemorrhagic stroke. Clin Chem Lab Med. 2009;47(12):1513-1518.19863297
41. Lee SY, Choi YC, Kim JH, Kim WJ. Serum neuron-specific enolase level as a biomarker in differential diagnosis of seizure and syncope. J Neurol. 2010 Oct;257(10):1708-1712.20532546
42. Shinozaki K, Oda S, Sadahiro T, et al. S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review. Crit Care. 2009;13(4):R121.19624826
43. Cheng F, Yuan Q, Yang J. Wang W, Liu H. The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review and meta-analysis. PLoS One. 2014 Sep 4;9(9):e106680.25188406


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
140624 Neuron-specific Enolase, Serum 57371-7 140690 Neuron-specific Enolase, Serum ng/mL 57371-7

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