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PubMed1996

Serum neuron specific enolase (S-NSE) reference interval evaluation by time-resolved immunofluorometry compared with a radioimmunoassay.

The serum neuron specific enolase (S-NSE; EC 4.2.1.11) reference interval was evaluated by DELFIA (Wallac) in 161 healthy blood donors and the method compared with the S-NSE RIA assay (Pharmacia). The DELFIA assay total analytical variation coefficient (CV%) was between 3.7% and 6.6%., the RIA CV% 7.6% to 13.1%. Late centrifugation (after hours) increased the variation as a result of contamination with blood cells. Log transformation into a gaussian distribution was selected by Box-Cox analysis and tested by two models: the gauss-distribution and the Refval transformation. The 95% reference intervals and corresponding 90% confidence intervals were: female 2.9-9.6 micrograms/l (2.6-3.2 and 8.5-10.7) micrograms/l and male 3.4-11.7 micrograms/l (3.0-3.8 and 10.2-13.2 micrograms/l). Mean values were significantly different (P < 0.001), female 5.3 (4.9-5.6), male 6.3 (5.8-6.7) micrograms/l. The serum NSE levels were analysed with both methods in a population of 110 patients. The results were significantly correlated (coefficient, 0.9896; r, 0.99; P < 0.0001-two tailed). For high S-NSE values (> 150.0 micrograms/l) differences between the methods exceeded the mean difference + 2S.D., while low concentrations were interconvertible. Maximal diagnostic efficacy was 0.91 for both assays, in DELFIA 17.2-23.9 micrograms/l and for RIA 17.2-21.9 micrograms/l. Identical sensitivity, specificity, discriminative power score, and likelihood ratio were found. The two methods are consequently interconvertible.

Adolescent↗
PubMed1985

Immunohistochemical demonstration of neuron-specific enolase in gynecologic malignant tumors.

Gynecologic malignant tumors were studied by the immunoperoxidase method for neuron-specific enolase (NSE). They included 22 argyrophil cell carcinomas of the endometrium, 6 argyrophil small cell carcinomas of the cervix, 21 argyrophil cell adenocarcinomas of the ovary (endometrioid type, 10; mucinous type, 11) and 3 ovarian carcinoids (strumal type, 2; insular type, 1). NSE was demonstrated in all cases of argyrophil small cell carcinomas of the cervix and ovarian carcinoids. On the other hand, NSE was positive only in four cases of endometrial carcinomas with argyrophil cells. Argyrophil cell adenocarcinomas of the cervix and the ovary were immunohistochemically negative for NSE. The current results suggest that argyrophil small cell carcinoma of the cervix, ovarian carcinoid, and some endometrial argyrophil cell carcinomas are related to APUDoma.

Adenocarcinoma↗
PubMed1994

Neuron-specific enolase as a marker of brain metastasis in patients with small-cell lung carcinoma.

Neuron-specific enolase (NSE) is one of the iso-forms of enolase, a glycolytic enzyme found in the neuroendocrine system. NSE is one of the most widely used tumor markers in small-cell lung carcinoma (SCLC). To assess the value of NSE in discriminating between the sites of metastases in SCLC-patients with and without cerebral involvement, serial NSE determinations were performed. Serum NSE was elevated in 76% of the patients at initial diagnosis. The value did not discriminate between the extent of disease nor between the sites of extrathoracic disease. NSE levels declined significantly at restaging. A persistent, significant rise occurred in patients with relapse of their disease, regardless of the site of relapse. In patients with brain metastases with and without extracranial disease at relapse, the NSE increase was significantly smaller than in patients without intracranial involvement. These findings indicate that serial determination of serum NSE in SCLC-patients may be useful in monitoring tumor activity but not in predicting the site of metastatic disease.

Adult↗
PubMed1995

Serum neuron-specific enolase and immunohistochemical markers of neuroendocrine differentiation in lung cancer.

An enzyme immunoassay for serum neuron-specific enolase (NSE) was evaluated with respect to analytical performance and clinical utility and compared with immunohistochemical evaluation of neuroendocrine differentiation. Values obtained agreed well with values obtained using a radioimmunoassay method giving a correlation coefficient of 0.934. Analytical performance of the enzyme immunoassay was good but the diagnostic sensitivity of 82% in extensive and 67% in limited disease was insufficient for serum NSE to be of value in the diagnosis of small cell lung cancer (SCLC). Serum NSE decreased significantly in 11 of 15 patients with SCLC following institution of chemotherapy. Classification of lung cancers into SCLC and non small cell lung cancer (NSCLC) types is largely based on tumour morphology. Neuroendocrine differentiation may not be morphologically evident. Immunohistochemical staining of tumour tissue with markers of neuroendocrine differentiation, i.e. NSE (both monoclonal and polyclonal antibodies) Leu 7, Chromogranin A and P G P 9.5 was performed in both patients with SCLC and NSCLC. 38 per cent of patients with NSCLC had both raised serum NSE and positive NSE (polyclonal) immunoperoxidase staining of lung tissue. A further 35 per cent of patients showed a raised serum NSE or positive immunohistochemistry but not both. The presence of two positive immunoperoxidase markers in lung tissue has been suggested as an indicator of responsiveness to chemotherapy in NSCLC patients. A number of factors may affect immunohistochemical positivity in tissue sections and the additional use of a serum marker may better define chemotherapy responsive groups.

Adult↗
PubMed1987

Serial determination of serum neuron-specific enolase in patients with neuroblastoma and other pediatric tumors.

The importance of determination of serum neuron-specific enolase (NSE) in patients with neuroblastoma has been emphasized by several authors. However, the specificity and sensitivity of NSE have not yet been well studied in tumors of infancy and childhood, nor is the role of serial determination of NSE in monitoring these patients fully understood. Concentrations of serum NSE were determined by a newly developed radioimmunoassay technique in 241 samples from 111 patients. NSE was also assayed in sera of nude mice bearing human pediatric tumors (16 samples), as well as in 30 tumor specimens. Eighty-two serum samples from 19 patients with neuroblastoma all showed NSE values (mean 120.2 ng/mL, range 16.2 to 722.0 ng/mL) elevated beyond the upper border of the normal range (14.6 ng/mL), even though four of the 19 patients had normal urinary excretion of 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA). Twelve of these patients were monitored with serial NSE determinations, and their serum NSE were found to correlate well with the tumor burden, but were transiently modified by chemotherapeutically induced cell death. All 68 samples from nine patients, free of neuroblastoma at assessment, showed NSE values within the normal range. Thirteen of 25 patients with tumors other than neuroblastoma, however, showed serum NSE values mildly elevated beyond the upper border of the normal range (mean of the 25 patients 36.7 ng/mL, range 5.0 to 234.0 ng/mL). Results from our nude mouse study and from NSE analysis of the tumor extracts paralleled the clinical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2003

Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC).

BACKGROUND: Neuron-specific enolase (NSE) is a well known marker of small cell lung cancer. The present study was designed to assess the clinical value of NSE in non-small cell lung cancer (NSCLC), as compared to that of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). METHODS: The study comprised 448 new consecutive NSCLC patients seen from 1996 to 2001. A set of 30 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was prospectively recorded for all patients. Patients were carefully followed-up, and their subsequent clinical course recorded. RESULTS: Increased values of NSE were present in 32% of the patients. Bivariate analyses showed that NSE, TPA and CEA were significantly correlated with each other, lactate dehydrogenase, tumour diameter, and disease extent. Univariate analyses showed that patients with elevated concentration of both NSE and TPA had significantly shorter survivals than patients with low values (30 [95% CI: 25-35] vs. 61 weeks [46-76], and 30 [CI: 24-36] vs. 59 weeks [40-79], respectively, P=0.0000). The Cox proportional hazards model including all the 22 variables significant in univariate analysis selected, in decreasing order of significance, the following variables: (1) N factor; (2) main treatment; (3) ECOG PS; (4) CNS metastasis; (5) age; (6) tumour cavitation; (7) NSE; (8) T factor; and (9) adrenal gland metastasis. CONCLUSIONS: This data indicates that serum assay of NSE is a useful marker also in NSCLC and a significant predictor of survival, independently of the other prognostic factors.

Adult↗
PubMed1996

Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation.

We have examined the regulation of neuron-specific gamma-enolase gene (NSE) expression in oligodendrocytes at various steps of their differentiation/maturation. We have demonstrated for the first time that NSE is expressed in oligodendroglial cells in vitro and in vivo, and only at a certain stage of differentiation. A heterogeneity of the gamma subunit was observed in cultured oligodendrocytes and the same one was found in adult rat brain. The level of gamma mRNA increased when precursor cells differentiated into oligodendrocytes. By contrast, no significant change in alpha-enolase gene expression was observed. High NSE (gamma gamma and alpha gamma) enolase activity was detected in cultured oligodendrocytes. Treatment with basic fibroblast growth factor, which stimulates the proliferation of oligodendrocyte precursor cells and reversibly blocks their differentiation, resulted in lower alpha gamma- and gamma gamma-enolase activities in these cells, but it enhanced alpha alpha-enolase activity slightly. These data indicate that gamma-enolase gene expression is associated with the differentiation of the oligodendrocytes and that it is repressed in adult fully mature cells.

Aging↗
PubMed1985

Molecular cloning and the nucleotide sequence of cDNA for neuron-specific enolase messenger RNA of rat brain.

The cDNAs to mRNA for rat gamma gamma enolase (neuron-specific enolase; NSE; EC 4.2.1.11) were isolated from a cDNA library by using differential colony hybridization and a hybrid-selected translation assay. By overlapping of the nucleotide sequences of several cDNA inserts, it was found that they spanned 2232 base pairs (bp) which included 1299 bp of the complete coding region, 68 bp of the 5' noncoding region, and 848 bp of the 3' noncoding region, including a polyadenylylation signal. In addition, the poly(A) tail was also found. The amino acid sequence deduced from the nucleotide sequence was composed of 433 amino acids. Southern blot analysis with a cDNA insert detected one hybridizing fragment in rat genomic DNA digested with several different restriction enzymes. Dot-blot and transfer hybridization analyses of poly(A)+ RNA from developing rat brains showed an increase of NSE mRNA 10-30 days after birth.

Amino Acid Sequence↗
PubMed2000

Comparison of Tc-99m sestamibi, serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy in small cell lung cancer.

Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are tumor markers of small cell lung cancer (SCLC) which were reported to predict outcome of patients with SCLC. We previously reported that dipyridamole-modulated Tc-99m sestamibi (dipyridamole-MIBI) single photon emission computed tomography (SPECT) could predict the response to chemotherapy in SCLC patients. The purpose of this study was to compare dipyridamole-MIBI and pretreatment serum levels of NSE and LDH for the prediction of response to chemotherapy in SCLC. Twenty-eight SCLC patients underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at lease two cycles). Serum levels of NSE and LDH were also measured at the same day of the imaging. Tomographic images before and after 0.84 mg/kg dipyridamole infusion were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete (CR), partial response (PR), no change (NC), and progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. Among the 28 patients, 15 were responders (2 CR, 13 PR) and 13 were nonresponders (11 NC, 2 PD). The change of tumor-to-normal lung ratio (T:NL) after infusion of dipyridamole was significantly higher in responders as compared with nonresponders (0.38 +/- 0.64 vs. -0.38 +/- 0.50, respectively, p = 0.002). However, pretreatment serum NSE and LDH levels did not correlate with the response to chemotherapy. Increase of T:NL after dipyridamole infusion was a strong negative predictor of chemotherapeutic response in SCLC patients, while NSE and LDH could not predict it.

Aged↗
PubMed1992

Expression of neuron-specific enolase immunoreactivity by cutaneous and extracutaneous Langerhans-cell histiocytoses ("X").

The immunohistochemical expression of Neuron-Specific Enolase (NSE) and of S100 protein was studied in 10 cases of cutaneous and 19 cases of extracutaneous Langerhans cell histiocytoses (LCH), including acute/proliferative forms (cutaneous Letterer-Siwe disease) and chronic/granulomatous forms (eosinophilic granuloma, Hand-Schüller-Christian disease). Of the LCH cases, 18 (62%) exhibited detectable NSE-immunoreactivity as compared to 82.8% for S100. NSE expression was found more frequently and intensely within acute (as compared to chronic) forms of LCH. This result lends further support to the cellular unicity of LCH, but also suggests some degree of heterogeneity among LCH cells. It can be speculated that NSE-expression is correlated with the proliferation/activation state of (abnormal) Langerhans cells.

Bone Diseases↗
PubMed1995

Cerebrospinal neuron-specific enolase, S-100 and myelin basic protein in neurological disorders.

In this study levels of neuron-specific enolase (NSE), S-100 protein (S-100) and myelin basic protein (MBP) in cerebrospinal fluid (CSF) of children and adults with distinct neurological disorders were examined. A previous study from our department demonstrated age related reference values for these brain-specific proteins in CSF. The median concentration level of the 3 proteins in 17 different neurological disease groups versus the reference group was compared. Significantly higher MBP values were observed in patients with multiple sclerosis (MS), cerebrovascular accident (CVA), metabolic disorder and infection. Furthermore, significantly higher values were demonstrated for S-100 in CVA and for NSE in metabolic diseases. In CVA, the NSE and S-100 values were significantly related with MBP values, whereas in MS the NSE and S-100 were not related with MBP values.

Adult↗
PubMed1999

Serum neuron-specific enolase in the major subtypes of status epilepticus.

OBJECTIVES: To determine the relative magnitudes of neuron-specific enolase (NSE) levels after complex partial status epilepticus (SE), absence SE, generalized convulsive SE, and subclinical generalized convulsive SE (frequently referred to as acute symptomatic myoclonic status epilepticus). BACKGROUND: NSE is a marker of acute brain injury and blood-brain barrier dysfunction, which is elevated in SE. METHODS: Serum NSE levels were drawn in 31 patients 1, 2, 3, and 7 days after SE. Patients were classified as acute symptomatic or remote symptomatic, and the duration and outcome of SE were determined and correlated with the peak NSE level. RESULTS: NSE was elevated significantly in all four subtypes of SE, but NSE levels were highest in complex partial and subclinical SE. The mean peak NSE level for the complex partial SE group was 23.88 ng/mL (n = 12), 21.5 ng/mL for absence SE (n = 1), 14.10 ng/mL for the generalized convulsive SE group (n = 12), and 37.83 ng/mL for the subclinical SE group (n = 6), all of which was significantly higher than normal control subjects (5.02 ng/mL). Outcome was significantly different between the three groups (p = 0.0007), and was significantly worse for subclinical SE (p = 0.0005, subclinical versus generalized convulsive SE). CONCLUSION: Serum NSE levels were highest in complex partial and subclinical generalized convulsive SE. The extremely high levels of NSE in subclinical SE reflect the severity of the acute neurologic insults and poor outcome common to subclinical SE. High NSE levels in complex partial SE reflects the long duration of SE in this subgroup, and potential for brain injury.

Electroencephalography↗
PubMed2002

Clinical roles of serum autoantibody against neuron-specific enolase in glaucoma patients.

In our recent papers, we found the presence of serum autoantibody against neuron specific enolase (NSE) in some glaucoma patients and suggested that this antibody might have significant roles in pathogenesis of glaucomatous optic neuropathy. In order to evaluate further the clinical roles of serum autoantibody against NSE in glaucoma, serum autoantibody against NSE was examined by western blot analysis and enzyme-linked immunosorbent assay (ELISA) in 4 patients with ocular hypertension (OH) and 242 patients with glaucoma (normal tension glaucoma [NTG], 73 cases; primary open angle glaucoma [POAG], 169 cases), and the relationships between the titers of anti-NSE antibody and clinical characteristics were evaluated. The titers of anti-NSE antibody showed a regular decreasing pattern with deteriorating visual field losses and glaucoma stages in POAG, especially early and late stages. However, no systematic pattern was observed in NTG. Although maximum and mean intraocular pressures (IOP)s and progression of visual field losses showed no correlation with the levels of serum anti-NSE antibody titers in either POAG or NTG, the anti-NSE antibody titers were relatively higher in NTG with visual field deterioration than in those without it. The present observations suggest that serum autoantibody against NSE may be clinically useful for diagnosing early stages of POAG, and for monitoring glaucoma progression of NTG.

Aged↗
PubMed2000

Significance of neuron-specific enolase levels before and during therapy for small cell lung cancer.

The level of serum neuron-specific enolase (NSE) has been implicated as a prognostic factor for patients with small cell lung cancer (SCLC). A prospective evaluation was undertaken to assess the prognostic significance of pretreatment NSE and treatment-induced minimum NSE values in patients with SCLC. Patients from two Phase III North Central Cancer Treatment Group trials [one for patients with extensive stage SCLC and one for patients with limited stage SCLC] were asked to enter this laboratory correlational trial. Both trials included treatment with four to six cycles of etoposide and cisplatin, and 121 patients (71 extensive stage SCLC and 50 limited stage SCLC) were entered into the present study of NSE. Pretreatment NSE values and treatment-induced minimum NSE values were independent predictors of time to progression and survival in multivariate analysis. Hazard rate modeling allowed the formulation of specific relationships of NSE to time to progression and survival. Pretreatment NSE levels inversely correlated with time to progression and survival in these patients with SCLC. Pretreatment NSE accounted for 28% of the variance in survival. Both pretreatment NSE and treatment-induced minimum NSE were independent prognostic predictors of time to progression and survival.

Adult↗
PubMed2000

[Study of plasma neuron-specific enolase activity of patients with chronic pulmonary heart disease complicated by pulmonary encephalopathy].

The plasma neuron-specific enolase (NSE) activity in the 15 patients of chronic pulmonary heart disease complicated by pulmonary encephalopathy and 10 chronic pulmonary heart disease without pulmonary encephalopathy (controls) were detected. The results showed that NSE activity in patients with moderate, severe pulmonary encephalopathy were significantly higher than those of patients with mild pulmonary encephalopathy, stable patients and controls. The plasma NSE activity from the patients with pulmonary encephalopathy were negatively correlated with the PaO2 and were positively correlated with PaCO2. This study suggests that plasma NSE activity may reflect the degree of brain damage by chronic hypoxia and remain of CO2 in the patients with chronic pulmonary heart disease.

Aged↗
PubMed2003

Significance of serum neuron-specific enolase in patients with acute traumatic brain injury.

OBJECTIVE: To study the association between serum neuron-specific enolase (NSE) and the extent of brain damage and the outcome after acute traumatic brain injury (TBI). METHODS: The release patterns of serum NSE in 78 patients after acute TBI were analyzed by using the enzyme linked immunosorbent assay. The levels of NSE were compared with Glasgow coma scale, the category of brain injury and the outcome after 6 months of injury. RESULTS: There were different NSE values in patients with minor (12.96 microg/L+/-2.39 microg/L), moderate (23.44 microg/L+/-5.33 microg/L) and severe brain injury (42.68 microg/L+/-4.57 microg/L). After severe TBI, the concentration of NSE in patients with epidural hematomas was 13.38 microg/L+/-4.01 microg/L, 24.03 microg/L+/-2.85 microg/L in brain contusion without surgical intervention group, 55.20 microg/L+/-6.35 microg/L in brain contusion with surgical intervention group, and 83.85 microg/L+/-15.82 microg/L in diffuse brain swelling group. There were close correlations between NSE values and Glasgow coma scale (r=-0.608, P<0.01) and the extent of brain injury (r=0.75, P<0.01). Patients with poor outcome had significantly higher initial and peak NSE values than those with good outcome (66.40 microg/L+/-9.46 microg/L, 94.24 microg/L+/-13.75 microg/L vs 32.16 microg/L+/-4.21 microg/L, 34.08 microg/L+/-4.40 microg/L, P<0.01, respectively). Initial NSE values were negatively related to the outcome (r=-0.501, P<0.01). Most patients with poor outcomes had persisting or secondary elevated NSE values. CONCLUSIONS: Serum NSE is one of the valuable neurobiochemical markers for assessment of the severity of brain injury and outcome prediction.

Acute Disease↗
PubMed1987

[Serum neuron-specific enolase (NSE) in patients with small cell lung cancer--comparison with carcinoembryonic antigen (CEA)].

Serum neuron-specific enolase (NSE) was determined by RIA in 102 lung cancer patients. Serum NSE was elevated (greater than 10 ng/ml) in 72% (21 of 29 cases) of small cell lung cancer (SCLC) patients, which was a significantly higher positive rate than those in normal adult controls (0%, 0/48), noncancerous lung disease (17%, 4/24), squamous cell carcinoma (19%, 6/31) and adenocarcinoma (16%, 4/25) (p less than 0.05, respectively). There were no NSE-positive cases in stage I-II lung cancer patients. In SCLC, cases of extensive disease had a significantly higher NSE-positive rate (100%, 8/8) than those of limited disease (62%, 13/21) (p less than 0.05), suggesting that NSE levels were related to the bulk of the tumor. There was an excellent correlation between serum NSE and clinical response. Raised NSE levels were identified significantly more frequently than those of CEA in SCLC before chemotherapy and on relapse (or progression) (p less than 0.025, p less than 0.005, respectively). Thus, serum NSE determinations may be more useful than those of CEA for the staging and monitoring of SCLC.

Adenocarcinoma↗