MUDr. Dana Maňasková

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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]


O úroveň výše

Poslední aktualizace: 16. 11. 2018 0:11:19
© Dana Maňasková, metabalance.cz
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