[Neuron-specific enolase (NSE)--a suitable tumor marker in malignant melanoma?]. / Neuronen-spezifische Enolase (NSE)--ein geeigneter Tumormarker des malignen Melanoms?

The neuron-specific enolase (NSE) level is elevated in neurons and in numerous cells of the APUD system; melanocytes are also considered to belong to this system. In order to test the relevance of NSE as a tumour marker for malignant melanoma, its concentration in serum was radioimmunologically determined in 89 patients with melanomas: 24 in stage I (primary tumours), 44 in stage II (regional metastases), and 21 in stage III (distant metastases). The average (+/- coefficient of variation) concentrations recorded were 7.4 micrograms/l (+/- 46%) in patients in stage I, 5.8 micrograms/l (+/- 32%) in those in stage II, and 11.0 micrograms/l (+/- 72%) in those in stage III. A threshold value of 11.5 micrograms/l was exceeded in 9 cases, including 8 patients in stage III. Since definitely increased values arose almost exclusively in distant metastases, determination of NSE levels in serum is hardly a suitable tool for early detection of latent metastases.

Solitary neuroendocrine cells and neuroepithelial bodies in the lower airways of embryonic, fetal, and postnatal sheep.

The sheep pulmonary intraepithelial APUD system was studied by histochemical, immunocytochemical, and electron microscopy techniques during different periods of lung development: embryonic, fetal (pseudoglandular, canalicular, and alveolar), and postnatal. The cells of the ovine pulmonary intraepithelial APUD system were found randomly distributed throughout the conducting and respiratory or undifferentiated airways. They appeared as isolated cells (solitary neuroendocrine cells) or in groups (neuroepithelial bodies). These cells were argyrophilic and immunoreactive for neuron-specific enolase but were not argentaffin. Ultrastructurally they were characterized by a basal position in the respiratory epithelium and by the presence of neurosecretory granules (dense-core vesicles) ranging between 65 and 230 nm of diametre. Quantitative studies showed that single neuroendocrine cells were more numerous in distal conducting airways and at fetal stages. The earliest identifiable argyrophilic and NSE-immunoreactive neuroendocrine cells in sheep airways appeared at gestational week 5, close to the term of the embryonic period.

Investigation on serum neurone-specific enolase in prostate cancer diagnosis and monitoring: comparative study of a multiple tumor marker assay.

A quadruple tumor marker serotest assay (neurone-specific enolase, NSE, prostate-specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino-embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28.6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonresponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE-positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE-positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision-making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.

High activity of mitochondrial glycerol phosphate dehydrogenase in insulinomas and carcinoid and other tumors of the amine precursor uptake decarboxylation system.

The activity of the mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5), the enzyme unique to the glycerol phosphate hydrogen shuttle, was measured in normal human tissues and tumors and compared with the activity of succinate dehydrogenase, another enzyme that transfers electrons to ubiquinone at site II of the electron transport chain. Six of 7 insulinomas and 10 of 12 carcinoid tumors showed high glycerol phosphate dehydrogenase activity. The activity was also increased in 3 of 4 gastrinomas, 2 paraganglionomas, 1 of 4 thyroid nodules, and 1 parathyroid tumor. These tissues belong to the amine precursor uptake decarboxylation system. The activity of glycerol phosphate dehydrogenase was generally unremarkable in non-amine precursor uptake decarboxylation system tumors and in normal tissues studied. However, 1 of 2 breast carcinomas, 1 submandibular tumor, and 2 of 3 melanomas were enriched in glycerol phosphate dehydrogenase activity. In general, succinate dehydrogenase activity exceeded that of glycerol phosphate dehydrogenase in all tissues except some of the tissues in which glycerol phosphate dehydrogenase activity was high. Normal tissues, such as the pancreatic beta-cell, which aerobically metabolize glucose rapidly utilize the glycerol phosphate shuttle to oxidize the large amount of NADH formed from glucose metabolism in the cytosol. Whether this is the reason for the enriched activity of the glycerol phosphate dehydrogenase in certain amine precursor uptake decarboxylation system tumors is unknown.

Immunocytochemical localization of aromatic L-amino acid decarboxylase in human, rat, and mouse bronchopulmonary and gastrointestinal endocrine cells.

Aromatic L-amino acid decarboxylase (AADC) catalyzes the cellular decarboxylation of L-aromatic amino acids and is therefore involved in the synthesis of several biogenic amines. Application of the indirect immunoperoxidase method on human, rat, and mouse tissues using specific antibodies to AADC revealed all AADC-containing cells. Besides mast cells and adrenergic nerve fibers, the following cells were immunostained: neuroendocrine cells in the tracheobronchial epithelium; neuroepithelial bodies in the bronchopulmonary epithelium; Kultschitzky cells in the small intestine and appendix as well as adrenal chromaffin cells. All the latter cells belong to the so-called APUD system, the "D" in the acronym standing for the activity of the enzyme aromatic L-amino acid decarboxylase. Immunocytochemistry for AADC may become an additional tool not only to highlight APUD cells in tissue sections but also to differentiate the sites of cellular amine synthesis from those of amine storage.

Development of neuroepithelial bodies and solitary endocrine cells in fetal rabbit lungs. II. Nonspecific esterase as an indicator of early maturation.

Activity for nonspecific esterases has been demonstrated histochemically in fetal rabbit lungs using alpha-naphthyl acetate as substrate. Commencing with a homogeneous distribution in pseudoglandular lungs, activity gradually heightens in the epithelium, progresses centrifugally along the bronchial tree, and reaches full expression in postnatal lungs, when most cells in conducting airways are strongly reactive. Well before this general rise, small clusters become conspicuously reactive in the epithelium, first in the larger bronchi and later in the smaller bronchi. At 25 days' gestation most of these are neuroepithelial bodies, which are recognizable in frozen sections and occur selectively near bronchial bifurcations. Subsequently, while the bodies formed earlier continue active, other clusters and solitary cells become reactive in more recently formed airways, amounting in all to 1-2% of the epithelial cells present. Near term these and the more organized neuroepithelial bodies occur throughout the bronchial tree up to the primitive respiratory zone. The small clusters and single cells may include some mature elements; however, as they generally correspond in incidence and distribution to clear cells and clusters, identified as precursors of neuroepithelial bodies, many are incompletely differentiated. Esterase activity, a characteristic shared with APUD cells in other organs, evidently rises about the time pulmonary endocrine cells become functional. Using the histochemical method, a large population of these cells is therefore demonstrable in lungs until after birth, when the increasing activity of nonendocrine cells finally obscures it.

Regulatory peptides and neuron-specific enolase in the respiratory tract of man and other mammals.

This short review deals with the distribution and cellular localization, in the respiratory tract, of five regulatory peptides (substance P, bombesin, vasoactive intestinal polypeptide (VIP), cholecystokinin, and somatostatin) and of a newly discovered neuroendocrine enzyme marker, neuron-specific enolase. Bombesin is found in typical mucosal endocrine cells, whereas the other regulatory peptides--principally substance P and VIP--are found, in significant concentrations, in autonomic nerves of the wall of the airways. Substance P, a putative sensory neurotransmitter, is found in autonomic nerves closely associated with the mucosal epithelium and the bronchial smooth muscle. VIP nerves, on the other hand, appear predominantly to innervate blood vessels, seromucous glands of the upper respiratory tract, and bronchial smooth muscle. The presence of neuron-specific enolase in both mucosal APUD cells and autonomic nerves has established this newly discovered neuronal enzyme as a useful marker for the entire neuroendocrine system of the lung and its derivative neoplasms.

Neuron specific enolase in human small cell carcinoma cultures.

Continuous cell lines of human lung cancers were analyzed for neuron specific enolase (NSE). The levels of NSE in the small cell carcinoma cells were in every case much higher than those derived from other forms of lung cancer. Since NSE is strictly localized to neurons and neuroendocrine cells of the amine precursor uptake and decarboxylation (APUD) series, the data provided further evidence that small cell carcinoma is an APUD cell tumor and is distinct from other forms of lung cancer.