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Neuron-Specific Enolase as an Immunohistochemical Marker Is Better Than Its Reputation.

ABSTRACT: The diagnosis of neuroendocrine neoplasms (NENs) may be challenging and is based on typical morphological features and positive staining for antibodies of neuroendocrine differentiation. Neuron-specific enolase (NSE) being a cytosolic marker may be useful in this setting. NSE is by many considered nonspecific, due to the finding of this marker in tumors considered not to be of neuroendocrine origin. Our aim was to determine whether this is true and whether NSE is more specific than previously realized. We examined 178 tumors (carcinomas and NENs) from breast, lung, stomach, and kidney using immunohistochemistry with the following markers: chromogranin A, synaptophysin, CD56, secretagogin, and NSE. Expression of NSE was compared with that of the other markers. NSE was expressed in 138 (78%) of all tumors. Of the NSE-expressing tumors, 95 (68%) cases expressed one or more additional neuroendocrine markers. The staining intensity and number of NSE-expressing tumor cells were highest among tumors of neuroendocrine origin and clear cell renal cell carcinomas. A positive association was found between NSE expression and the number of additional neuroendocrine markers expressed in each of the tumors. Practically all tumors positive for an accepted neuroendocrine marker also expressed NSE.

SUBMITTER: Mjones P

PROVIDER: S-EPMC5714096 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Neuron-Specific Enolase as an Immunohistochemical Marker Is Better Than Its Reputation.

Mjønes Patricia P Sagatun Liv L Nordrum Ivar S IS Waldum Helge L HL

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20171003 12

The diagnosis of neuroendocrine neoplasms (NENs) may be challenging and is based on typical morphological features and positive staining for antibodies of neuroendocrine differentiation. Neuron-specific enolase (NSE) being a cytosolic marker may be useful in this setting. NSE is by many considered nonspecific, due to the finding of this marker in tumors considered not to be of neuroendocrine origin. Our aim was to determine whether this is true and whether NSE is more specific than previously re ...[more]

PMID: 28972818

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Project description:ObjectivesWe aimed to determine if elevations in serum neuron-specific enolase are associated with brain injury and outcomes in adults who require venoarterial extracorporeal membrane oxygenation.DesignProspective observational study.SettingTwo ICUs of a university hospital, Paris, France.PatientsConsecutive adult patients treated with venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock or in-hospital refractory cardiac arrest.InterventionsNone.Measurements and main resultsSerum sampled 1, 3, and 7 days after venoarterial extracorporeal membrane oxygenation cannulation was stored at -80°C and neuron-specific enolase concentrations were measured in batches at the end of the study. The association between neuron-specific enolase concentrations and outcomes (28-d mortality and poor outcome, defined by a score of 4-6 on the modified Rankin scale at 90 d) were explored by multivariable logistic regression, with neuron-specific enolase concentrations dichotomized according to median values. One-hundred three patients were included, of whom 26 (25%) received preextracorporeal membrane oxygenation cardiopulmonary resuscitation. Median (interquartile range) day-1, day-3, and day-7 neuron-specific enolase serum concentrations were 37 μg/L (26-51 μg/L), 25 μg/L (19-37) μg/L, and 22 μg/L (17-31 μg/L). After adjustment for Simplified Acute Physiology Score II, preextracorporeal membrane oxygenation cardiopulmonary resuscitation, and Sepsis Organ Failure Assessment score at time of cannulation, a day-3 neuron-specific enolase greater than 25 μg/L remained independently associated with 28-day mortality (adjusted odds ratio, 4.98; 95% CI, 1.86-13.32) and poor outcome at 90 days (adjusted odds ratio, 4.63; 95% CI, 1.81-11.84). A day-3 neuron-specific enolase threshold greater than 80 μg/L had a 100% specificity for prediction of both mortality (95% CI, 92-100%) and poor functional outcome (95% CI, 89-100%). In a subset of patients who underwent brain CT, neuron-specific enolase concentrations were significantly higher in patients diagnosed with stroke, as compared with those without stroke.ConclusionsIn adult patients under venoarterial extracorporeal membrane oxygenation, day-3 serum neuron-specific enolase concentrations are independently associated with short-term mortality and poor functional outcomes. These findings deserve validation in a multicenter setting.

Project description:Autism spectrum disorder (ASD) is an important health issue and affects 1 in 59 children in the US. Prior studies determined that maternal autoantibody related (MAR) autism is thought to be associated with ~23% of ASD cases. We previously identified seven MAR-specific autoantigens including CRMP1, CRMP2, GDA, LDHA, LDHB, STIP1, and YBX1. We subsequently described the epitope peptide sequences recognized by maternal autoantibodies for each of the seven ASD-specific autoantigens. The aim of the current study was to expand upon our previous work and identify additional antigens recognized by the ASD-specific maternal autoantibodies, as well as to map the unique ASD-specific epitopes using microarray technology. Fetal Rhesus macaque brain tissues were separated by molecular weight and a fraction containing bands between 37 and 45 kDa was analyzed using 2-D gel electrophoresis, followed by peptide mass mapping using MALDI-TOF MS and TOF/TOF tandem MS/MS. Using this methodology, Neuron specific enolase (NSE) was identified as a target autoantigen and selected for epitope mapping. The full NSE sequence was translated into 15-mer peptides with an overlap of 14 amino acids onto microarray slides and probed with maternal plasma from mothers with an ASD child and from mothers with a Typically Developing child (TD) (ASD = 27 and TD = 21). The resulting data were analyzed by T-test. We found 16 ASD-specific NSE-peptide sequences for which four sequences were statistically significant (p < 0.05) using both the t-test and SAM t-test: DVAASEFYRDGKYDL (p = 0.047; SAM score 1.49), IEDPFDQDDWAAWSK (p = 0.049; SAM score 1.49), ERLAKYNQLMRIEEE (p = 0.045; SAM score 1.57), and RLAKYNQLMRIEEEL (p = 0.017; SAM score 1.82). We further identified 5 sequences that were recognized by both ASD and TD antibodies suggesting a large immunodominant epitope (DYPVVSIEDPFDQDDWAAW). While maternal autoantibodies against the NSE protein are present both in mothers with ASD and mothers of TD children, there are several ASD-specific epitopes that can potentially be used as MAR ASD biomarkers. Further, studies including analysis of NSE as a target protein in combination with the previously identified MAR ASD autoantigens are currently underway.

Dataset Information

Neuron-Specific Enolase as an Immunohistochemical Marker Is Better Than Its Reputation.

Publications

Neuron-Specific Enolase as an Immunohistochemical Marker Is Better Than Its Reputation.

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