Zvýšené hladiny a jejich význam u konkrétních stavů
False low results
Presence of extremely high NSE concentrations ("hooking")
Autoantibodies to NSE
Presence of heterophile antibodies
Islet cell tumors
- Typically less than 40% of cases [8]
Lung carcinoma
- BAL NSE is a better predictor of malignancy than serum NSE.
- Measurements of serum NSE increases its sensitivity
- Specificity remains unchanged
- No correlation exists between
- BAL NSE and
- Serum NSE
- Tumor size
- Nodal status
- Presence of metastases [12]
- BAL fluid measurements of NSE may have diagnostic value
- Specially if it is simultaneously measured in the serum
- No correlation with serum NSE Cancer 1996;77:2039-43 [12]
NSE-secreting neoplasms
- NSE 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 [8]
PNT + Lung cancer
- NSE levels were determined by ELISA in the sera of
- 100 prostate cancer
- 47 Hodgkin lymphoma
- 35 lung cancer
- 35 peripheral nerve tumor patients
- 132 healthy controls [11]
- Median levels of serum NSE were elevated in
- Lung cancer (p=0.018) [11]
- Peripheral nerve tumors (p=0.008) [11]
- In prostate cancer and Hodgkin lymphoma
- Higher than the controls but nostatistically significant difference (p>0.05) [11]
Pleural effusion
- Cross-sectional study 93 patients with pleural effusions
- 44 malignant
- 49 benign [10]
- NSE and CA 15-3 serum and pleural levels were measured simultaneously
- CA 15-3 serum
- Sensitivity 70.4%
- Specificity 49.0% [10]
- CA 15-3 pleural
- Sensitivity 79.5%
- Specificity 49.0% [10]
- Serum NSE
- Sensitivity 75.0%
- Specificity 69.4% [10]
- Pleural NSE
- Sensitivity 75.0%
- Specificity 73.5%
- Accuracy of 74.2% - highest diagnostic potential [10]
- Combination NSE and CA 15-3
- Serum and pleural levels
- Highest sensitivity- 93.2% [10]
- Serum levels
- Lowest sensitivity (47.7%) [10]
- A malignant pleural effusion represents an advanced malignancy disease which is associated with high mortality
- Pleural fluid aspiration and cytological examination
- Main diagnostic method for determining pleural fluid characteristics
- At ideal settings has a sensitivity of 60% (Sriram et al., 2011) [10]
- Presence of tumor cells in pleural effusion is a diagnostic marker of malignant pleural effusion
- Probability of finding them is low
- More likely is to find the factors secreted by tumor in the pleural fluid or serum (M Li et al., 2014; Xu, Yu, Zhan and Zhang, 2014) [10]
Solid-cystic (papillary cystic) tumour of the human pancreas
- Immunoreactivity to neuron specific enolase (NSE) demonstrated
- Employing immunohistochemical methods
- Positive staining for NSE was found with two different antisera
- Failed to detect any hormonal products or neuroendocrine granules in the tumour
- Caution in using the enzyme as a differential diagnostic tool, especially in surgical pathology of epithelial pancreatic neoplasms occurring in young females
- Electron microscopy will be necessary
- Solid-cystic tumours of the pancreas consistently show large intracytoplasmic zymogen-like granules [10]
Adenokarcinom ledvin
Adenokarcinomy ledvin
Apudom
Biotin
- Vzorky by neměly být odebrány pacientům podstupujícím léčbu s vysokými dávkami biotinu (tj. > 5 mg/den)
- Po dobu nejméně 8 hodin od podání poslední dávky biotinu [5]
Carcinoid tumor
Carcinoids
- Up to 66% of cases have elev. NSE [8]
Outcome predictors of coma
- Glasgow coma scale
- Other clinical predictors (papillary light responses, corneal reflexes, motor responses to pain, myoclonus, status epilepticus)
- Electroencephalogram
- Sensory evoked potentials
- Elevated NSE
- Indicative of a poor outcome
- Qualitative or semi-quantitative fashion [8]
Elevated NSE supports clinical suspection
- +NSE suggests an underlying small cell lung carcinoma (SCLC) in:
- Patient with a lung mass
- Disseminated malignancy of unknown origin
- Symptoms suggestive of paraneoplastic disease without identifiable tumor [8]
- Elevated serum NSE supports the clinical suspicion:
- No clear elevations in the primary tumor markers + clinical suspection on:
- Carcinoid
- Islet cell tumor
- Neuroblastoma [8]
Carcinoid
- Chromogranin A
- Urinary 5-hydroxyindoleacetic acid
- Serum/blood 5-hydroxytryptamine [8]
Islet cell tumors
- Variety of peptide and amine-derived hormones
- Chromogranin A [8]
Neuroblastoma
- Vanillylmandelic acid
- Homovanillic acid [8]
Endokrinní nádory pankreasu
Falešně pozitivní výsledky
Oddělení séra do 1h
- Stanovení přednostně v séru
- Protože je NSE i v červených krvinkách a krevních destičkách !!
- Provést oddělení krevních elementů nejpozději do 1hod od odběru !!
- Jinak jsou naměřené hodnoty falešně pozitivní
Hemolýza
- Koncentrace NSE se falešně zvýší
- Uvolněním NSE z erytrocytů
- Nepoužívat opakované rozmrazení a zmrazení vzorku [1]
- Interferenci způsobuje již obsah hemoglobinu vyšší než 50 mg/l [1]
- Hemoglobin concentrations as low as 20 mg/dL were found to have an adverse effect on NSE testing [8]
Proton pump inhibitor treatment
Hemolytic anemia
Hepatic failure
End stage renal failure
After epileptic seizure
Encephalitis
Stroke
Rapidly progressive dementia
Hirschsprung’s disease (HD)
- Most common cause of neonatal intestinal obstruction
- Presence of aganglionosis from seromuscular or full thickness biopsy
- Mucosal-sub mucosal biopsy is more intended becouse of complications
- Interpretation of hematoxylin and eosin (H&E) + acetylcholine esterase often problematic
- Neuron-specific enolase staining (NSE) is an available and easy [13]
- 65 mucosal-submucosal and 65 seromuscular rectal biopsies (standard) obtained from the patients suspected of HD
- Stained by NSE and H&E staining was used for seromuscular samples
- Sensitivity 100%, specificity 84.2%, efficiency 89.1%, positive 81.8% and negative 100% predictive values in the diagnosis of HD in NSE method (p<0.05)
- Evaluation of hypoganglionosis
- One false-negative
- Nine false-positive [13]
- Finding ganglion cell
- Definitely rules out HD
- Lack of ganglion cell
- Confirms 81.8% of H.D cases [13]
Karcinom ledvin
Koncentrace NSE v likvoru
- Zvýšené u onemocnění, která vedou k neuronální destrukci
- Rychle progredující demence typu Creutzfeldt-Jacob disease (CJD)
- Prognostický marker u traumatu CNS
- Hodnoty v likvoru korelují s outcomem u pacientů v kómatu [4]
- Metastázy SCLC do CNS
- Obzvláště při zasažení leptomening [4]
- Po recentním epileptickém záchvatu
- Encefalitidy
- CMP
- U NSE-sekretujících tumorů [4]
Maligní nádory neurálního a neuroendokrinního původu
Malobuněčný karcinom - plicní forma
- Cca 1/4 všech plicních karcinomů
- Většinou velmi sensitivní na chemoterapii a ozařování
- Nejlepší kombinací pro sledování malobuněčného karcinomu
- TPA a NSE
Medulární karcinom
Medullary thyroid carcinoma
Meduloblastom
Melanom
Nemaligní onemocnění plic (mírné zvýšení)
Neural crest-derived tumors
- Frequently overexpressed by [8]
Neuroblastom
- Exact frequency of NSE expression unknown [8]
NET of the gastrointestinal tract
- 39 patients
- 3 gastric
- 13 intestinal carcinoid tumors
- 6 gastrinomas
- 3 insulinomas
- 1 glucagonoma
- 2 mixed islet cell tumors
- 11 neuroendocrine pancreatic carcinomas
- 15 healthy subjects
- 15 nonendocrine gastric, pancreatic, and intestinal tumors [5]
- 36 of the 39 patients elevated circulating levels of NSE
- Values below 12 ng/ml
- Healthy subjects
- Nonendocrine tumors
- 2 insulinomas
- 1 gastrinoma [5]
- No significant difference of serum NSE was found
- Between 23 'functioning' and 16 'nonfunctioning' NET
- 14 of the NET were malignant
- NSE circulating values were significantly higher than those of nonmalignant forms [5]
- After curative surgery
- Serum NSE decreased significantly [5]
- NSE can be considered a reliable marker:
- In the differential diagnosis between endocrine and nonendocrine neoplasms
- Clinical detection of silent endocrine tumors
- Follow-up of NET [5]
Neuroendocrine tumours
- Circulating neuron-specific enolase (NSE) and chromogranin A (CgA) were measured in
- NSE normal pod 12.5 microg/l
- Chromogranin A normal pod 100 microg/L [7]
- 128 patients with neuroendocrine tumours (NET) without renal insufficiency
- 99 gastroenteropancreatic (GEP) NET
- 19 medullary thyroid carcinoma
- 10 phaeochromocytoma
- 53 non-NET were studied as controls [7]
- NSE elevated in 48 (38%) of the 128 NET patients
- Specificity of 73% [7]
- CgA elevated in 76 (59%) of the 128 NET patients
- Specificity of 68%
- CgA proved to be more sensitive than NSE [7]
- Immunostaining for NSE
- Positive in 3/8 of controls with elevated CgA levels
- Immunostaining for CgA and synaptophysin
- Negative in all cases [7]
- Elevated CgA levels
- Significantly associated with two independent parameters
- Presence of other secretions (P = 0.0001)
- Heavy tumour burden (P = 0.001) [7]
- Elevated NSE levels were exclusively associated with
- Poor tumour differentiation (P = 0.01) [7]
- CgA appeared to be a better marker of tumour evolution than NSE [7]
Neuronal injury
- Prognostic marker in neuronal injury
- Elevated serum NSE levels correlate with a poor outcome in coma
- In particular when caused by hypoxic insult [8]
Pancreatic disorders and Neuron-specific enolase and CA 19-9
- Neuron-specific enolase as a marker for islet cell and nerve tissue.
- Pancreatic tissues from patients with
- Insulinoma
- Nonfunctioning islet cell tumor
- Chronic pancreatitis
- Pancreatic adenocarcinoma
- 5 normal patients [6]
- Neuron-specific enolase was localized in
- Nerve fibers
- Normal islet cells
- Islet cell tumors [6]
- Concentration was elevated
- Only in the tissue of islet cell tumors
- In serum from patients with insulinoma
- Pancreatic tissue of pancreatitis or pancreatic adenocarcinoma
- Various changes in acini and islets were present [6]
- Neuron-specific enolase is a good marker for islet cell tumor
- Valuable for examining islets in pancreas with various disorders
- Both alone and in combination with other tumor markers [6]
Carbohydrate antigen 19-9
- Localized in all the carcinoma cells in the pancreatic tissue
- In some of the normal pancreatic ducts
- No cells were simultaneously immunostained by anti-neuron-specific enolase and anti-carbohydrate antigen 19-9 antibodies [6]
Pancreatic islet cell cancer
Pituitary adenomas
- 36 patients
- 24 women
- 12 men
- 19 tumors secreted prolactin (PRL)
- 6 growth hormone (GH)
- 11 were NF adenomas
- 28 Control subjects without known pituitary disorders
- 9 females
- 19 males [9]
- Complete pituitary function test
- Serum PRL, GH, corticotropin and (or) cortisol, thyrotropin, free thyroxine, lutropin, testosterone or estradiol-17ß, and follitropin
- Normal NSE values were pod 12.5 ug/L [9]
- Mean (±SD) serum NSE concentration
- Significantly higher in tumor patients x controls
- 7.5 ± 2.9 ug/L (range 1.0–16.5 ug/L) x 5.0 ± 1.5 ug/L (range 2.3–9.9 ug/L) (P <0.001) [9]
- Patients with tumors
- Serum NSE concentrations within the reference interval in all but one subject
- Mean serum NSE concentration was also significantly higher (P <0.003) in each subgroup of pituitary tumor group when compared with the control group [9]
- PRL, GH, and NF tumors
- Values were 6.9 ± 2.6 ug/L (range 1.0–12.0 ug/L), 8.1 ± 1.7 ug/L (range 5.7–10.0 ug/L), and 8.3 ± 3.7 ug/L (range 4.5–16.5 ug/L)
- Mean serum NSE concentrations were similar among the three subgroups of tumor patients
- No significant correlation was found between serum PRL and NSE concentrations in patients with PRL adenoma [9]
- NSE is not a useful marker of pituitary adenomas [9]
- Cannot distinguish among PRL, GH, and NF tumors [9]
Predikce prognózy CNS po srdeční zástavě
- Klíčová pro následující, terapeutický přístup
- 96 pacientů po KPR (průměrný věk 63,7; 78% muži)
- V úvodu léčených terapeutickou hypotermií na cílovou TT 33°C po dobu 24 h
- Odběr krve k stanovení NSE 1., 2., 3. a 4. den po přijetí
- Neurologický stav sme hodnotili pomocí cerebral performance categories (CPC)
- Optimální cut off hodnota NSE stanovená
- 1. den pro predikci CPC 1-2 pod 22,28 ug/l (senzitivita 94,4; specifita 59,09 ; P=0,0002)
- 2. den pro predikci CPC 1-2 pod 27,6 ug/l (senzitivita 91,89; specifita 80,77; P<0,0001)
- 3. den pod 24,2 ug/l (senzitivita 97,37; specifita 85,71; P<0,0001)
- 4. den pod 20,84 ug/l (senzitivita 94,29; specifita 93,75; P<0,0001)
- Měření NSE lze využít pro predikci prognózy po srdeční zástavě i u nemocných léčených v úvodu přesnými metodami kontroly tělesné teploty
- Největší výtěžnost mělo stanovení NSE provedené 4. den po srdeční zástavě
- Těsně následované 3. dnem
- Hodnota větší nad 50,2ug/l byla spojená se 100% specifitou pro špatnou prognózu
Rapidly progressive dementias
- Elevated CSF concentrations support the diagnosis
- Creutzfeldt-Jacob Disease etc. [8]
Seminomy
Small cell lung carcinoma (SCLC)
- Up to 70% of patients have elevated serum NSE concentrations at diagnosis
- Approximately 90% of patients with advanced SCLC will have serum levels above the healthy reference range [8]
- Prospective evaluation
- Phase III North Central Cancer Treatment Group trials
- Assess the prognostic significance of pretreatment NSE and treatment-induced minimum NSE values in patients with SCLC
- Treatment with four to six cycles of etoposide and cisplatin
- 121 patients (71 extensive stage SCLC and 50 limited stage SCLC)
- Pretreatment NSE values
- Inversely correlated with time to progression and survival in these patients with SCLC [11]
- Accounted for 28% of the variance in survival
- Treatment-induced minimum NSE values
- Independent prognostic predictors of time to progression and survival [11]