Tumor markers neuron-specific enolase

The usual carcinoid tumor is sofid and yeUow-tan in appearance. Tumor cells exhibit a monotonous morphology, with pink granular cytoplasm and round nuclei with infrequent mitoses. Most carcinoids can be recognized by their reactions to silver stains and to neuroendocrine cell markers, such as chromogranin and neuron-specific enolase. Ultra-structuraUy, carcinoids possess numerous membrane-bound, electron-dense neurosecretory granules. These granules contain peptide hormones and bioactive amines, which can occasionally be identified by immunocytochemi-cal techniques. 

Attempts are being made to identify more sensitive and specific markers for carcinoids. For example, measurement of chromogranin A in serum is reported to be more sensitive than urinary 5-HIAA in detecting carcinoid tumors and may reflect tumor size, but specificity is lower. Plasma levels of neuron-specific enolase, neuropeptide K, and substance P have also been suggested as diagnostic and prognostic markers in carcinoid tumors. 

Immunohistochemical staining is fairly consistent and straightforward in ONE. The tumor cells are positive for synaptophysin and neuron-specific enolase and, occasionally, for chromogranin (Fig. 9.5). Up to 30% of cases may be positive for CAM 5.2. However, ONEs are uniformly negative for epithelial membrane antigen, muscle markers, and CD 99 (MIC-2). Elongated cells often observed at the periphery of the lobules, so-called sus-tentacular cells, are positive for S-100 protein and glial fibrillary acidic protein (Fig. 9.6, Tables 9.4 and 9.5). 

The tumors are positive for synaptophysin, chromogranin, and neuron-specific enolase and may express a variety of hormones (growth hormone, prolactin, TSH, ACTH, and FSH). A few are hormone negative and are designated as null-cell adenomas. Almost all are positive for CAM 5.2, either focally or diffusely, and about half are positive for AE 1/3. They are negative for cytokeratin 7, 19, and 20, as well as S-100 protein. Pituitary transcription factor-1 is selectively expressed in tumors that express growth hormone, prolactin, and TSH. No diagnostic molecular markers are currently in use for sporadic pituitary lesions. ... 

These three neuroendocrine tumors of the larynx all display positivity for typical neuroendocrine markers such as chromogranin, synaptophysin, and neuron-specific enolase. They may also be positive for carcinoembryonic antigen (CEA) or epithelial membrane antigen (EMA). Atypical carcinoid and SCNEC can also express other neuroendocrine markers such as serotonin, calcitonin, and somatostatin. TTE-1 is probably not a useful marker to distinguish metastatic pulmonary small cell carcinoma from primary tumors in the head and neck because up to 50% of extrapulmonary small cell carcinomas are positive for TTR-l.i 8... 

FIGURE 10.38 Distribution of markers in pancreatic endocrine tumors. SYN, synaptophysin NSE, neuron-specific enolase LMWCK, low-molecular-weight cytokeratin CgA, chromogranin A PC2, pro-convertase 2 PCM, peptidylglycine alpha-amidating enzyme PC3, proconvertase 3 NFP, neurofilament protein HCC(a), human chorionic gonadotropin alpha VIM, vimentin. 

Nash SV, Said JW. Gastroenteropancreatic neuroendocrine tumors. A histochemical and immunohistochemical study of epithelial (keratin proteins, carcinoembryonic antigen) and neuroendocrine (neuron-specific enolase, bombesin and chromo-granin) markers in foregut, midgut, and hindgut tumors. Am J Clin Pathol. 1986 86 415-422. 

Inhibin A is also a sensitive marker of Sertoli cell differentiation (>90% positive). Sertoli cell tumor including its large cell calcifying variant stains variably positive with antibodies to vimentin, cytokeratin, S-100, synaptophy-sin, chromogranin, and neuron-specific enolase. Cytokeratin immunoreactivity in Sertoli cell tumors is usually stronger than that seen in Leydig cell tumors. Immunoreactivity for FLAP is not seen in Sertoli cell tumors. 

Neuroblastic tumors express neuronal markers of varying sensitivity and specificity neuron-specific enolase, leu-7, protein gene product 9.5, synaptophysin, chromogranin, and other markers. 

While neuron-specific enolase (NSE) has been described as a marker of neuronal tumors in reviews and texts, this author finds that it has better uses than this. The shortcoming for neuronal tumors is its propensity to also stain glial tumors, which commonly need to be distinguished from neuronal tumors. 7 Experimental IFIC stains such as Neu-N identify neurons by showing their on-target nuclear features rather than their cytoplasmic or confusing surface features. " 425 cases refractory to immu-nohistochemical stains, electron microscopy positively identifies Nissl substance, neurofilaments, neurosecretory granules, and synapses in neoplastic cells. 

Detection of Micrometastases and Circulating Tumor Cells of Tumors with Neuroendocrine Diflerentiation, PNET and Small Cell Carcinoma of the Lung by Amplification of Neuroendocrine-Specific Markers mRNA Chromogranin A, Neuron-Specific Enolase, Choline Acetyltransferase, Secretogranin II and Somatostatin Receptor Type 2... 

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