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]