Diagnostic value of α-enolase expression and serum α-enolase autoantibody levels in lung cancer / Valor diagnóstico da expressão de α-enolase e dos níveis séricos de autoanticorpos contra α-enolase no câncer de pulmão

ABSTRACT Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

RESUMO Objetivo: Investigar o valor diagnóstico da α-enolase (ENO1) e dos níveis séricos de autoanticorpos contra ENO1 no câncer de pulmão. Métodos: Marcação imuno-histoquímica e ELISA foram realizados para detectar a expressão de ENO1 no tecido pulmonar e os níveis séricos de autoanticorpos contra ENO1, respectivamente. Resultados: A expressão de ENO1 foi maior nos tecidos de câncer de pulmão que nos tecidos de doença pulmonar benigna (p < 0,001). Não houve diferença significativa entre os diversos grupos de classificação patológica quanto à proporção de amostras de câncer de pulmão que expressaram ENO1. A proporção de amostras que expressaram ENO1 foi maior nos pacientes com câncer de pulmão nos estágios I/II que naqueles com câncer de pulmão nos estágios III/IV (χ2 = 5,445; p = 0,018). Não houve relação entre a expressão de ENO1 em tecidos de câncer de pulmão e idade, sexo ou histórico de tabagismo. Os níveis séricos de anticorpos contra ENO1 foram significativamente maiores no grupo câncer de pulmão que nos grupos doença pulmonar benigna e controle (p < 0,001). As diferenças entre os grupos de classificação patológica não foram estatisticamente significativas. Os níveis séricos de anticorpos contra ENO1 foram também significativamente maiores nos pacientes com câncer de pulmão nos estágios I/II que naqueles com câncer de pulmão nos estágios III/IV (p < 0,01). Nos pacientes com câncer de pulmão, não houve relação entre os níveis séricos de anticorpos contra ENO1 e idade, sexo ou histórico de tabagismo. A curva ROC do diagnóstico de câncer de pulmão baseado nos níveis de anticorpos contra ENO1 apresentou área sob a curva = 0,806. Conclusões: Nossos resultados sugerem que há relação entre níveis elevados de ENO1 e o estágio clínico do câncer de pulmão e que a expressão de ENO1 e os níveis séricos de autoanticorpos contra ENO1 têm valor diagnóstico no câncer de pulmão.

Congenital epulis.

Congenital epulis of the newborn is a very rare and unique tumor first described in 1871 by Neuman. It has a female predilection. It is a tumor with no tendency to recur after excision. The histogenesis of the lesion is unknown, but it is believed to be of mesenchymal origin. We report a 2-day-old female with tumor mass on the anterior mandibular alveolar ridge, which demonstrated immunoreactivity for vimentin, S-100 and neuron-specific enolase; thus, suggesting a similar histogenesis with granular cell tumor.

Enolasa específica de neurona en dos recién nacidos con depresión ligera al nacer / Neuron- specific enolase in two newborns presenting with moderate depression at birth

La enolasa específica de neurona es una isoenzima que se vierte al torrente sanguíneo después de un episodio de daño neuronal. En los procesos de hipoxia neonatal estos valores enzimáticos en suero suelen estar alterados. El objetivo del presente artículo fue estudiar la enolasa específica de neurona en suero de 2 recién nacidos con Apgar bajo y determinar si, en el seguimiento durante un año, dichos pacientes presentaban trastornos del desarrollo psicomotor. MÉTODOS. Se tomaron muestras de suero al momento del nacimiento y a las 72 h siguientes. Se determinaron los niveles de enolasa específica de neurona por un método inmunoenzimá tico de tipo ELISA. Cada muestra fue evaluada por el método de reacción en cadena de la polimerasa para citomegalovirus, en el Instituto de Inmunología de Wuersburg (Alemania). También se cuantificaron anticuerpos contra citomegalovirus de clase IgM e IgG, en el Laboratorio de Neuroquímica de la Universidad Georg August de Goettingen (Alemania). Se recogieron los datos clínicos de interés de cada recién nacido y al a±o se citaron a estos pacientes y se les realizó un examen físico para evaluar su neurodesarrollo. RESULTADOS. Las cifras de enolasa estuvieron incrementadas tanto al nacimiento como a las 72 h, con anticuerpos anticitomegalovirus de clase IgG que fueron transferidos de la madre a través de la placenta. No se encontró presencia de este virus en el momento del nacimiento. En el examen físico y neurológico realizado al año se constató que los niños evolucionaban satisfactoriamente hasta esa fecha. CONCLUSIONES. Se recomienda extender el estudio hasta los 3 años de vida y aumentar el número de pacientes estudiados, con énfasis en aquellos casos cuyo Apgar es menor de 5 a los 5 min del nacimiento.

Neuron-specific Enolase of is an isoenzyme present in blood stream after a neuronal damage episode. In processes of neonatal hypoxia, these enzymatic values in serum may be altered. The aim of present paper was to study Enolase specific of neuron in the serum of two newborns with low Apgar score and to determine if, during a one year follow-up, such patients presented disorders of psychomotor development. METHODS: We took serum samples at birth and at 72 hours. Levels of Enolase specific of neuron by immunoenzymatic method type ELISA were determined. Each sample was assessed by polymerase chain reaction (PCR) to cytomegalovirus in Wuersburg Institute of Immunology (Germany). Also, we quantified antibodies to IgM and IgG cytomegalovirus in Neurochemistry Institute of Georg August of Goettingen University (Germany). Interesting clinical data of each newborn were collected and after a year, all these patients were cited for a physical examination to evaluate tits neurodevelopment. RESULTS: Enolase figures were increased both at birth and at 72 hours, with IgG anticytomegalovirus antibodies from mother through placenta. At birth there was not presence of this virus. At physical and neurological examination performed at 1 year it was possible to confirm that children evolved adequately until now. CONCLUSIONS: Study must to be prolonged until 3 years of life, and to increase number of study patients, emphasizing on those with an Apgar score lower than 5 at 5 minutes post-birth.

Establishment of Reference Intervals of Tumor Markers in Korean Adults / 대한진단검사의학회지

BACKGROUND: The sensitivity and specificity of tumor markers for detecting cancer could be significantly changed by the reference intervals of tumor markers. We established reference intervals of tumor markers in Korean adults and evaluated its importance, since the reference intervals recommended by the manufacturers were determined in the Caucasian population and have sometimes been adopted without verification. METHODS: We established the reference intervals of alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)125, carbohydrate antigen (CA)19-9, total prostate specific antigen (TPSA), cytokeratin fragment (Cyfra)21-1, and neuron specific enolase (NSE) according to the CLSI guideline in a maximum number of 1,364 healthy adults aged 20-60 yrs who visited a health promotion center from January to February 2007. RESULTS: Reference intervals of all tumor markers except for AFP were not in agreement with those recommended by the manufacturers. Reference intervals of CEA, TPSA, CA19-9, CA125, and Cyfra21-1 were age dependent. The mean reference values of NSE, CA125, and CEA were statistically different according to gender (11.72 vs 10.78 ng/mL), menopause status (18.89 vs 12.62 U/mL), and smoking status (2.60 vs 2.12 vs 1.80 ng/mL for smokers, past smokers, and non-smokers, respectively),respectively. CONCLUSIONS: With the verification and establishment of reference intervals of tumor markers in a Korean local population, we found the reference intervals significantly different by either age, gender, smoking or menopause status.

A case of rhabdomyosarcoma masquerading as acute leukemia at presentation: a case report.

Non-hematopoietic malignancies infiltrating bone marrow have always been a source of erroneous diagnosis. Among these, the small round cell tumors like neuroblastomas and rhabdomyosarcomas mimick the hematopoietic blasts. Several case reports of rhabdomyosarcoma mimicking acute leukemia, clinically and morphologically at presentation have been reported in the literature. To the best of our knowledge such an entity has not been reported in Indian literature. We report here one such case of alveolar rhabdomyosarcoma masquerading as acute leukemia. A thorough clinical examination with high degree of suspicion on bone marrow morphology and judicious use of appropriate immunohistochemistry markers will solve many of these cases.

Fine needle aspiration cytology of breast carcinoma with neuroendocrine features--a case report with histopathological and immunohistochemical correlation.

Cytohistological and immunohistochemical features of a rare case of breast carcinoma with diffuse neuroendocrine features occurring in an elderly female patient is reported. Cytology demonstrated predominantly single and loose clusters of monomorphic plasmacytoid tumor cells that possessed moderate amounts of basophilic cytoplasm with eccentrically placed nuclei. These cells were also showing conspicuos rosette like formations. Histological examination showed a typical endocrine pattern with organoid nests and ribbons of well differentiated monomorphic cells with frequent pseudorosette formation resembling carcinoid tumor of gastrointestinal tract. Neuroendocrine differentiation was confirmed by immunohistochemical positivity for neuron specific enolase, synaptophysin and chromagranin.

Extrapulmonary Small Cell Carcinoma of the Liver: Clinicopathological and Immunohistochemical Findings

Patients with primary small cell carcinoma of the liver have rarely been described in medical literature. Knowledge of clinical, pathological and immunohistochemical properties remains limited. We described an 82-year-old female patient with primary small cell carcinoma of the liver. Histologically, the tumor showed typical morphology of a pulmonary small cell carcinoma. Immunohistochemically, the tumor revealed neuroendocrine differentiation; positive reaction for chromogranin, synaptophysin, CD56, and neuron specific enolase. The tumor was also positive for TTF-1 and c-kit but completely negative for hepatocyte, carcinoembryonic antigen, cytokeratin 7; 19; and 20. Herein, we discussed the clinical, pathological and immunohistochemical findings of extrapulmonary small cell carcinoma of the liver and reviewed the relevant literature.

Marcadores de diferenciação endócrina para diagnóstico do carcinoma de pequenas células extra-pulmonares / Markers of endocrine differentiation in extra-pulmonary small cell carcinoma

Introducao: estudos recentes confirmam a natureza endocrina do carcinoma indiferenciado de pequenas celulas do pulmao bem como das suas apresentacoes extra-pulmonares. O objetivo do estudo foi comparar a utilidade da Protein Gene Peptide com a enzima enolase neuronio especifica (NSE) o hormonio adrenocorticotropico e a calcitonina na diferenciacao endocrina do carcinoma indiferenciado de celulas extra-pulmonares. Materiais e metodos: analise de dados primarios nao publicados. A tecnica imunohistoquimica utilizada foi atraves do metodo peroxidase-antiperoxidase utilizando anticorpos PGP, NSE, ACTH e calcitonina...

Non increased neuron-specific enolase concentration in cerebrospinal fluid during first febrile seizures and year follow-up in pediatric patients

Febrile seizures are the commonest acute neurological disorder of early childhood. Studies suggested that febrile seizures are previous acute events from a more serious neurological problem. Due to neuron-specific enolase is generally accepted as a marker for neuropathological processes in the brain, 16 pediatric patients were studied during their first seizures and a year after it. Neuron-specific enolase in cerebrospinal fluid and blood were analysed by an immune enzyme assay. Non pathological neuron-specific enolase values were obtained in both periods in the group of patients. There no significative differences when paired series statistics test was performed with 95 per cent of confidence. Neuron-specific enolase appears not to be a marker for febrile seizures because its concentration not be increased in cerebrospinal fluid in this group of patients.

Neuron-specific enolase is a useful marker of neuroendocrine origin in pheochromocytoma cell culture

Neuron-specific enolase (NSE) has been used as a marker for neuroendocrine tumors either in immunocytochemical studies or in serum measurements. ln this paper NSE levels were determined in cultured pheochromocytoma cells to test whether it is also a useful marker ín cell culture of tumors derived from neuroendocrine system. Cultured pheochromocytoma cells came from a primary explant and were grown in RPMI supplemented with 20 per cent fetal calf serum, 100 mug/mL ampicillin and 100 mug/mL streptomycin. NSE was measured in culture medium and cell homogenates. Samples from different pheochromocytoma cultures were analyzed and compared to normal cultured fibroblast cells derived from human skin. NSE was measured by a commercially available radioimmunoassay kit. NSE levels were higher in cell homogenates as compared to those in culture medium, reaching levels as high as 6-fold in the former in TE cell line (26.46 ng/mL and 4.39 ng/mL respectively. Serial NSE measurements in culture medium from TE cell line evidenced decreasing values in subsequential subcultures (from 9.24 ng/mL during primary explant to 1.7 ng/ml. in the 10th subculture). In cultured normal fibroblasts, NSE levels in cultured media were definitely lower than those obtained from pheochromocytoma cultures. These preliminary data suggest that NSE may be a useful marker of neuroendocrine derived tumors, such as pheochromocytoma, in culture. Thus, the simplicity and availability of NSE radioimmunoassay provides an alternative to catecholamine measurement to better characterize pheochromocytoma cell lines in culture, with the advantage of faster results at lower costs.

Choroid plexus tumours--an immunohistochemical analysis with review of literature.

Immunohistochemical analysis of 9 choroid plexus papillomas (CPPs) and 3 choroid plexus carcinomas (CPCs) using a panel of antibodies against glial fibrillary acidic protein (GFAP), cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, vimentin (vim), and neuron specific enolase (NSE) is presented. Focal positivity was observed for GFAP in 11, vimentin in 7, cytokeratin in 2 and EMA in 3 cases. Diffuse and intense immunoreactivity for S-100 protein was seen in all papillomas, however, unreactive areas were noted in carcinomas. All cases exhibited focal to diffuse NSE positivity. Location and type of the tumour and age of the patient did not influence the staining pattern except for predominant S-100 positivity in papillomas. The significance of these findings is discussed in relation to the differential diagnosis or immunoreactivity patterns of these tumours.

Identificaçäo da proteina S-100, da enolase neurônio-específica e do gangliosídeo GD3, em melanomas / Identification of S-100 protein, neuron-specific enolase and GD3 gangliosides in melanomas

Os autores procuraram localizar nas células de melanoma a proteína S-100, a enolase neurônio-específica e o gangliosídeo GD3 (Mel-1), através da técnica da imunoperoxidase (PAP). Realizaram o estudo em 38 casos de melanoma clínica e histologicamente classificados como: melanoma superficial extensivo, 19 casos, e melanoma nodular, 19 casos. Os pacientes apresentaram idade variável de 17 a 78 anos; 35 eram brancos e um pardo, sendo 24 do sexo masculino e 14 feminino. A presença nas células tumorais dos antígenos pesquisados näo revelou qualquer correlaçäo com o sexo, idade e o tipo histogenético. Demonstraram a existência de associaçäo significativa da co-expressäo aos pares dos antígenos celulares: proteína S-100 e Mel-1; proteína S-100 e enolase neurônio-específica