Reactivity For Neuron-specific Enolase Research Articles

Zinc Gluconate Supplementation Protects against Methotrexate-induced Neurotoxicity in Rats via Downregulation of Oxidative Stress, Inflammation and Neuron-specific Enolase Reactivity in Rats

Background: The global increase in the incidence of cancers, as well as neurotoxicity induced by cancer therapy, has necessitated research into agents that are neuroprotective without impeding cancer treatment. Objective: The objective of this study is to investigate the neuroprotective effects of feed-added zinc on methotrexate-induced changes in rats. Methods: Animals were grouped into normal control and methotrexate control, which were fed rodent chow and three groups fed zinc gluconate incorporated into the diet at 25, 50 and 100 mg/kg, respectively. Animals in the first group, in addition to normal diet, received intraperitoneal (i.p.) injections of saline at 2 ml/ kg, while rats in the four other groups were administered methotrexate i.p. at 20 mg/kg/day on the last three days (19-21) of the experiment. On day 22, rats were exposed to the behavioural paradigms, following which they were euthanised and blood was taken for biochemical assays. Sections of the hippocampus were homogenised for the assessment of neurotransmitters or processed for histological and immunohistochemical studies. Results: Dietary zinc supplements at certain concentrations protected against the development of methotrexate-induced alteration in body weight, food intake, memory histomorphology, and neuron- specific enolase reactivity. Conclusion: Conclusion: Dietary zinc supplementation was protective against neurotoxicity induced following methotrexate administration, with possible mechanisms being the down-regulation of oxidative stress, inflammation and neuron-specific enolase reactivity.

A case of hepatic carcinoid in a red deer hind (Cervus elaphus)

A carcinoid tumour in the liver of a red deer hind (Cervus elaphus) is described. Macroscopically, the liver was considerably enlarged with multifocal, firm, yellow and red nodular neoplastic masses, which were histopathologically diagnosed as hepatic carcinoids. The diagnosis was confirmed by modified Grimelius staining, which demonstrated numerous small argyrophilic granules in the cytoplasm of neoplastic cells, and by immunohistochemistry. The neoplastic cells gave a strong positive reaction for neuron-specific enolase (NSE) and synaptophysin and a weak positive reaction for chromogranin A. To our knowledge, this is the first report of a hepatic carcinoid in red deer.

Central neurocytoma in the vermis of the cerebellum

In neuropathology, anatomic landmarks and topographic relationships bear particularly on issues of differential diagnosis. A case of central neurocytoma of the vermis of the cerebellum is being reported in this article. A 45-year-old male with features of hydrocephalous and a posterior fossa space-occupying lesion was diagnosed as having central neurocytoma upon a microscopy of Hematoxylene and Eosin stained sections. The diagnosis was confirmed by a positive immunohistochemical reaction for Neuron Specific Enolase (NSE) and Synaptophysin. This case report is being made to emphasize that a high index of suspicion is required even for reporting neuropathology where the site does not match the conventional location of the lesion seen and also to emphasize the importance of immunohistochemistry in proving such unusually located lesions.

Frequent expression of neuroendocrine markers in mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a new tumorous entity which has been recently established. In this article, we examined the expression of neuroendocrine markers including neuron specific enolase (NSE), chromogranin A and synaptophysin in 16 cases of MTSCC using immunohistochemistry. The sex ratio (male: female) of the patients was 4:12. In normal kidney, distal tubules or collecting ducts were positive for NSE, but no structures were positive for chromogranin A or synaptophysin. All MTSCCs showed a positive reaction for NSE. Additionally, fifteen of sixteen neoplasms (93.8%) with MTSCC showed the expression of either chromogranin A or synaptophysin or both. Finally, it is possible that MTSCC may be one of renal neoplasms which frequently exhibit the neuroendocrine differentiation.

Oral alveolar soft-part sarcoma: Review of literature and case report with immunohistochemistry study for prognostic markers

To describe a case of alveolar soft-part sarcoma (ASPS) affecting the tongue of a child and to study prognostic imunohistochemical markers for the disease. Tissue sections were incubated with primary antibodies reactive to neuron-specific enolase (NSE), vimentin, desmin, S-100 protein, cytokeratins AE1-AE3, EMA, neurofilament, synaptophysin, and muscle-specific actin (MSA), and for prognostic markers, including Ki-67, p53, bcl-2, bax, and nm23. Histologically, the tumor showed a proliferation of large polygonal cells with PAS-positive diastase-resistant intracytoplasmatic material, arranged in an alveolar growth pattern. Diffuse positive reaction for neuron specific enolase (NSE), focal reactivity for desmin and S-100 protein, strong positivity for nm23 and bax, but weak reaction for p53 and Ki-67 were found. No bcl-2-positive cells were noted. These immunohistochemical findings may reflect the less aggressive behavior of ASPS in oral tissues.

Subtypes of thymic epithelial cells defined by neuroendocrine markers.

The study attempted to define characteristics of thymic epithelial cells within rat thymus based on the expression of neuroendocrine markers. Using an immunohistochemical approach, the following markers were localised: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE) and chromogranin A (ChA). It was shown that cells displaying immunostaining typical for individual markers reside in distinct regions of the thymus and represent subtypes within various populations of thymic epithelial cells. An immunoreactivity for PGP 9.5 was found exclusively in a subtype of cortical epithelial cells, located mostly within the inner zone of the cortex. On the other hand, NSE represented a marker of most epithelial cells located in the medulla. Few such cells which were negative for NSE proved positive for ChA. Among the cells with a strong reaction for NSE some cells also manifested a positive reaction for ChA. While the pattern of neuroendocrine marker distribution may reflect functional properties of thymic epithelial cells which might be different within distinct areas of the thymus, the differential expression of individual markers seems to reflect biological activity of the cells and/or distinct stages of their differentiation.

Expression of neuropeptides and other neuroendocrine markers in human phaeochromocytomas

Aims: Phaeochromocytomas may produce several neuropeptides as they are considered neuroendocrine tumours. Nevertheless, studies are scarce and no clear predictive biologic value has been stablished in the case of neuropeptides expression.Methods: We have investigated immunohistochemically the neuropeptides expression of a serie of 36 phaeochromocytomas: 25 sporadic, seven familial type MEN (multiple endocrine neoplasm) and four familial phaeochromocytomas not associated with MEN syndrome. The reactivity for neuron-specific enolase (NSE), synaptophysin, vasoactive intestinal peptide (VIP), chromogranin A, calcitonin, ACTH, somatostatin and HMB-45 was tested according to the avidin-biotin complex (ABC) method using polyclonal antibodies.Results: Phaeochromocytomas have a multiple synthetic activity as main neuroendocrine feature. Despite phaeochromocytoma tumour cells heterogeneity chromogranin and synaptophysin are the most common neuropeptides synthesised, as they are associated with the presence of neuroendocrine storage granules. We find a statistically significant higher synthesis of corticotrophin hormone in familial phaeochromocytomas than in sporadic forms, on the contrary the synthesis of VIP is statistically associated with sporadic forms of phaeochromocytomas. We also found a direct relation of ACTH and overexpression and malignant tumours and a positive relationship between NSE and benign forms of phaeochromocytomas.

上咽頭平滑筋肉腫例

Leiomyosarcoma arising in the pharynx is very rare. Notably, there have been no reports of leiomyosarcoma of the epipharynx. We describe the first reported case of epipharyngeal leiomyosarcoma. The patient was a 59-year-old male who had the sensation of a foreign body in the pharyngolaryngeal area, probably due to collar fixation under orthopedic treatment. He was referred to the Department of Otolaryngology where he underwent fiberscopic examination of the pharyngolarynx. A tumor the size of a soybean had developed in the Rosenmuller fossa of the epipharynx and showed polypoid proliferation. The tumor did not exhibit reactivity for neuron specific enolase, neurofilament protein, chromogranin, S-100 protein, glycogen, keratin, a-SMA or alcian blue, but was markedly positive for vimentin. Electron microscopic observation demonstrated myofilaments with dense patches, subplasmalemmal plaque and a basal lamina which were characteristic of smooth muscle. On the basis of immunopathological and microscopic findings, this case was diagnosed as a leiomyosarcoma. After local excision of the tumor using a KTP laser, CYVADIC chemotherapy, followed by radiation therapy of 40 Gy was performed. There has been no evidence of recurrence since the patient was released from the hospital.

Gastrointestinal Autonomic Nerve Tumors A Clinicopathological, Immunohistochemical, and Ultrastructural Study of 12 Cases

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor of the intestinal tract and retroperitoneum first described by Herrera and associates in 1984. Distinction of GAN tumors from other gastrointestinal stromal tumors is based on electron microscopic findings. Thus far there have been 12 reported cases. We present an additional 12 GAN tumors, identified by us during 4 years. There were seven male and five female patients and they ranged in age from 10 to 85 years (mean: 58 years). Sites of the tumors were stomach (three), jejunum (two), ileum (four), mesentery (one), and retroperitoneum (two). Eight of the tumors measured > 10 cm in greatest dimension. Usually well circumscribed, the neoplasms were tan to light pink, sometimes hemorrhagic, and soft. There was a variety of histologic patterns including fascicles, palisades, and whorls. Mitotic activity varied from 0 to 23 mitosis per 10 high-power fields (HPF). Using a panel of 10 immunohistochemical stains, only vimentin was consistently positive. There was neuron-specific enolase reactivity in six and S-100 protein reactivity in two cases. All muscle markers were negative. Ultrastructural studies showed neuron-like cells with long axonic cytoplasmic processes ending in bulbous synapse-like structures containing dense-core neurosecretory granules and clear vesicles. Basement membrane was absent. These features are reminiscent of ganglia of the intestinal autonomic nervous system. The patients were followed for 5-125 months (mean of 26 months). Tumor recurred or metastasized to the liver in seven patients (58%) and four patients died with tumor. There were correlations between tumor size (> 10 cm), mitotic count (at least five per 10 HPF), and aggressive behavior.

Nerve sheath myxoma (neurothekeoma) of the skin: light microscopic and immunohistochemical reappraisal of the cellular variant*

Nerve sheath myxoma (NSM) is a rare cutaneous neoplasm, the histogenesis of which is controversial. Fifteen cases of NSM were studied by routine light microscopy and with a broad panel of immunohistochemical stains. NSM were classified into three groups based on cellularity, mucin content and growth pattern. 1) The hypocellular (myxoid) type (5/15 cases) showed frequent encapsulation or sharp circumscription. Immunohistochemically this type was strongly positive for S-100 protein and collagen type IV and variably positive for epithelial membrane antigen. 2) The cellular type (4/15 cases) had scant mucin and ill-defined nodular or infiltrating growth. Immunostaining showed positive reaction for neuron specific enolase (2/4), Leu-7 (1/4) and smooth muscle specific actin (2/4), and was negative with the other antibodies. 3) The "mixed type" (6/15 cases) had variable cellularity and mucin content with poor demarcation and variable immunolabeling. We conclude that: 1) there are major light microscopic and immunohistochemical differences between the classical hypocellular (myxoid) and the cellular forms of NSM (neurothekeoma); 2) while the immunohistochemical results support the presence of nerve sheath differentiation in the classical forms of NSM, and to some extent in the mixed forms, there is an absence of convincing evidence of neural differentiation in the cellular variant by either light microscopy or immunohistochemistry; 3) the variable immunophenotypes suggest that differentiation other than neural may take place in CNT.

Atypical basal cell hyperplasia of the prostate. Immunophenotypic profile and proposed classification of basal cell proliferations.

Prostatic basal cell proliferations range from focal basal cell hyperplasia (BCH) to florid adenoid basal cell tumor (ABCT). We reviewed 36 cases of basal cell proliferation to evaluate the architectural and cytologic spectrum of these lesions and identified four distinct patterns by light microscopy: BCH, 12 cases, including two cases with stromal sclerosis; atypical BCH with nucleolomegaly, eight cases; basal cell adenoma (BCA), nine cases; and ABCT, seven cases. Twenty-three cases were evaluated immunohistochemically, and all displayed cytoplasmic immunoreactivity in basal cells with basal-cell-specific high-molecular-weight keratin 34 beta E12 but with increased staining in BCH compared with that in BCA and ABCT. Prostate-specific antigen and prostatic acid phosphatase reactivity were seen at least focally in all cases except two cases each of BCA and ABCT. Chromogranin, S-100 protein, and neuron-specific enolase reactivity were rare or negative in all cases. Nucleolar diameter, measured in 18 of the 36 cases, was significantly greater in atypical BCH (mean, 1.96 microns) than in other forms of basal cell proliferation (mean, < 1.0 microns) (P < 0.05). These results indicate that on the basis of light microscopic, immunohistochemical, and morphometric findings, the spectrum of basal cell proliferations in the prostate can be separated into four distinct groups: BCH, atypical BCH, BCA, and ABCT.

Amelanotic Malignant Melanoma of the Esophagus: Case Report and Review of the Literature

A case of amelanotic malignant melanoma of the esophagus in a 76-year-old woman is reported. A whitish polypoid tumor, measuring 3 x 2 x 2.7 cm, surrounded by black pigmented mucosa, was detected in the middle intrathoracic esophagus. The tumor showed a lobulated surface lined by squamous cell layer, and had epithelioid and polyhedral cells forming alveolar clusters. Melanin pigments or stainability for the dihydroxyphenylalanine (DOPA) reaction were only observed in a few tumor cells. Junctional changes and mucosal melanosis, however, were found freely in the mucosa around the tumor. Many tumor cells showed a strongly positive immunohistochemical reaction for neuron specific enolase (NSE) and S100 protein. The patient died of widespread metastases six months after surgery. Further, a review of 106 reported cases of primary esophageal malignant melanoma, including 29 autopsies, was made; the melanomas were found to include 10 of amelanotic type, eight of which had been misdiagnosed at biopsy. Junctional changes could be found in the mucosa over or around the tumor, in four cases, and mucosal melanosis in one. Lymph node metastasis was the most frequently observed development at autopsy regardless of whether the tumor was amelanotic or melanotic. For correct diagnoses of melanomas of the amelanotic type, peripheral mucosal findings, such as junctional changes or melanosis, should be helpful; and, in order to obtain a good prognosis, a careful resection of the regional lymph nodes could prove valuable.

Small cell undifferentiated (‘neuroendocrine’) carcinoma of the colon

Three patients are described who presented with a large colonic adenoma in which a solid, undifferentiated carcinomatous component was found on microscopic examination. Despite small size (1.0 and 1.5 cm) and submucosal location in two cases, the tumours had metastasized to regional lymph nodes and the liver and death ensued at 4, 11 and 18 weeks after surgery. Immunocytochemistry was positive for carcino-embryonic antigen, low molecular weight cytokeratins and neuron specific enolase in all three cases and scanty dense core granules of neurosecretory type were found in one of two examined by electron microscopy. These 'neuroendocrine' carcinomas are compared with 'pure' adenomas and 'ordinary' poorly differentiated adenocarcinomas of the colon from which they differ, mainly by lack of glandular differentiation and mucus secretion, although two adenocarcinomas also showed patchy reactivity for neuron specific enolase. The term 'neuroendocrine' may be disputed but is now well established to describe a tumour that runs a uniquely aggressive course and for which radical surgery alone cannot provide a cure.

Immunohistochemical Characterization of Rat Central and Peripheral Nerve Tumors Induced by Ethylnitrosourea

Ethylnitrosourea-induced central and peripheral nerve tumors in Sprague-Dawley rats were tested for GFAP (Glial Fibrillary Acidic Protein), S-100 protein, NSE (Neuron Specific Enolase) and Anti-Leu 7 (HNK-1) immunoreactivity utilizing the ABC method (avidin-biotin-complex) for GFAP, S-100 protein and NSE, and the PAP method (peroxidase-antiperoxidase) for Anti-Leu 7. Peripheral nerve neurinomas were consistently positive for S-100 protein and consistently negative for GFAP and Anti-Leu 7. Neurinomas would occasionally exhibit positive staining for NSE (2 of 55 tumors). The staining intensity for S-100 protein varied from strongly positive in differentiated neurinomas to weakly positive in anaplastic tumors. Neoplastic and reactive astrocytes exhibited positive staining for both S-100 protein and GFAP. Variation in the GFAP staining intensity of glial tumors correlated with the degree of differentiation as anaplastic tumors did not stain with the same intensity as their more differentiated counterparts. Oligodendrogliomas exhibited occasional immunoreactivity to S-100 protein (3 of 36 tumors). NSE reactivity in oligodendrogliomas was rarely observed (1 tumor in 36) and immunoreactivity against GFAP or Anti-Leu 7 was consistently absent. Anti-Leu 7 and NSE proved to be of little value in the classification of ENU-induced neural tumors.

The Epithelium of the Human Endolymphatic Sac: Immunohistochemical Characterization (With 1 color plate)

A panel of monoclonal and polyclonal antibodies has been used to study the epithelium of the extraosseous part of the human endolymphatic sac (ES) by immunohistochemistry. The ES epithelium reacted with several epithelial markers such as Lu-5, different anticytokeratins, antiepithelial membrane antigen, and anticarcinoembryonic antigen. Unexpectedly, all epithelial cells also revealed a strong positive reaction for the mesenchymal marker vimentin and for S-100 protein. 'Neuroendocrine', a neurosecretory antigen, and neuron-specific enolase reactivity was detected in a few epithelial cells. The results support the assumption that the ES epithelium is metabolically active and capable of secretion and resorption. These findings are in keeping with results of functional experiments in animals. The demonstration of neurosecretory antigen and neuron-specific enolase in some cells indicate that the epithelium may also have paracrine functions.

Intraventricular Neurocytoma: A Report of Two Cases

Intraventricular neurocytoma is a rare clinicopathological entity that has been recently recognized. Previous reports have not described the magnetic resonance imaging findings of this tumor. This paper describes two patients with neurocytoma in which serpiginous flow voids and isointensity with cortex were distinctive features on the magnetic resonance imaging scan. Immunohistochemical studies showed reactivity for neuron-specific enolase, Leu-7, and S-100 protein.

Brenner tumor of the ovary: A correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuronspecific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

Undifferentiated small round‐cell tumors of childhood: The immunocytochemical demonstration of myogenic differentiation in fine‐needle aspirates

The recognition of myogenic differentiation is not always possible using routine light or electron microscopic techniques. In this article, we describe our experience with two small round-cell neoplasms occurring in young children, each of which exhibited an undifferentiated light microscopic appearance. In both cases, myogenic features were revealed by immunocytochemical methods applied to fine-needle aspiration (FNA) biopsies. Each was immunoreactive for desmin and vimentin and failed to react with antibodies to leukocyte-common antigen. Moreover, formalin-fixed tissue sections of one case were negative for cytokeratin and epithelial membrane antigen. Sporadic reactivity for neuron-specific enolase and Leu-7 antigen was observed in occasional cells in FNA specimens, but synaptophysin was not identified. The rapidity of the method and the reliability of the immunocytochemical findings, when compared with routine cytologic evaluation, emphasize the diagnostic utility of immunocytochemical analysis when FNAs of pediatric soft-tissue tumors are obtained.

Primary gastric peripheral T-cell malignant lymphoma with helper/inducer phenotype.First case report with a complete histological ultrastructural and immunochemical study

Primary gastrointestinal T-cell malignant lymphomas (T-ML) are very rare. In this case report we describe a primary gastric tumor with local lymph node involvement. On the basis of histologic, immunohistochemical, and electron microscopic studies, the authors classified this tumor as a pleomorphic T-ML, large cell variant with peripheral helper/inducer T-cell phenotype (Leu1/CD5+, Leu4/CD3+, Leu5/CD2+, Leu9/CD7+, and Leu3/CD4+). The extreme pleomorphism of lymphoma cells, the numerous giant cells, and the presence of tumor nodules with two or three concentric layers were the three striking morphologic features of our case. Tumor cells showed an inconstant but true positive staining with anti-LeuM1/CD15 and LeuM3/CD14 antibodies. Vimentin positivity could be related to the presence of intermediate filaments at ultrastructural level. Neuron-specific enolase reactivity was a peculiar but unexplained feature. Furthermore, the positivity of the surface markers Ki-1/CD30, anti-Tac/CD25 and HLA-DR, and the nuclear marker Ki-67 suggested an activation state and a high proliferative activity of the tumor cells. This study emphasizes the usefulness of combined pathologic methods in order to rule other diagnoses such as undifferentiated carcinoma, malignant melanoma, malignant histiocytosis, B-cell lymphoma and interdigitating reticulum cells sarcoma, in view of an extremely polymorph tumor proliferation. This is apparently the first completely documented case report of a primary gastric pleomorphic T-ML of peripheral T-cell origin.

Alveolar soft part sarcoma. An immunohistochemical, cytologic and electron-microscopic study and a quantitative DNA analysis.

The type, differentiation and histogenesis of the tumor cells of alveolar soft part sarcoma (ASPS) have been analyzed in a series of ten cases by a light-microscopic, ultrastructural, immunohistochemical and cytologic investigation and quantitative DNA analysis. Four tumors deviated from ordinary ASPS: three were wholly or partly of the so-called pleomorphic variant of ASPS and a fourth tumor showed calcifications of the psammoma body type. The ultrastructural findings and immunohistochemical demonstration of desmin supported the hypothesis of a rhabdomyomatous differentiation and gave no support to epithelial (negative immunoreactions for cytokeratins, epithelial membrane antigen, HMFG-1 and -2, tissue polypeptide antigen (TPA] or neuroectodermal (negative for S-100 protein, glial fibrillary acidic protein, neurofilaments) differentiation. The negative immunoreactions for vimentin and myoglobin and the positive reaction for neuron specific enolase (NSE) do not exclude a rhabdomyomatous differentiation since in rhabdomyosarcomas the undifferentiated rhabdomyoblasts generally contain vimentin and the differentiated tumor cells contain myoglobin and rhabdomyosarcoma has previously been reported as being positive for NSE. The production of external lamina material peripherally in the tumor cell nests and around vessels in the vascular septa was demonstrated both ultrastructurally and by immunohistochemistry using antibodies against collagen IV and laminin. The cytologic appearance in smears obtained by fine-needle aspiration from a case of the pleomorphic variant showed some resemblance to that of a carcinoma. The seven tumors with an ordinary cell appearance were found to show a diploid DNA-distribution at a quantitative analysis performed on paraffin sections, while the three tumors wholly or partly of the pleomorphic type showed an additional tetraploid peak.