Neuron-Specific Enolase (NSE)

Sources/Clones
Accurate (BBSNCU1), American Research (5G10, NH3), Axcel, Biodesign (MIG-N3, 5E2), Biogenesis (BG10), Biogenex (MIG-N3), Biotec (XNE12), Cymbus Bioscience (5E2), Dako (BBS-NC, VI-H14), Immunotech, Novocastra (VI-H14, SE2), Research Diagnostics (5E2, 5G10, 5A4), Sanbio (MIG-N3), Seralab (MIG-N3), Serotec (MIG-N3), Shandon (BBS-NC, VI-H14) and Zymed.

Fixation/Preparation
Both polyclonal and monoclonal antibodies are immunoreactive in routinely prepared tissue sections. Immunostaining is enhanced by HIER.

Background
Neuron-specific enolase (NSE) is the glycolytic isoenzyme of the enolaseg-g dimer specifically detected in neurons and neuroendocrine cells, and their corresponding tumors (Wick et al, 1983; Venores et al, 1984). In addition, NSE has been demonstrated in the non-neoplastic cells of the pituitary, peptide-secreting tissues, pinealocytes, neuroendocrine cells of the lung, thyroid, parafollicular cells, adrenal medulla, islets of Langerhans, Merkel cells of the skin (Leong et al, 1986) and melanocytes. NSE immunostaining is also positive in normal striated muscle, hepatocytes and, to a lesser extent, smooth muscle (Cooper, 1994).
While highly sensitive, NSE has low specificity. Antibodies to NSE enjoyed great popularity in the earlier days of diagnostic immunohistochemistry as markers of neural and neuroendocrine differentiation. However, it was soon realized that most anti-NSE preparations showed a high rate of unwanted crossreactivities even among the monoclonal antibodies and a high level of background staining often made interpretation difficult. NSE has since become known facetiously as ''non-specific enolase" (Bjerkehagen et al, 1994). While its application in immunohistochemistry is limited, assays for NSE are increasingly being performed as diagnostic and prognostic markers in the serum, pleural effusions and cerebrospinal fluid in cases of head injury, status epilepticus, small cell carcinoma of the lung, neuroblastoma, various neuroendocrine tumors, germ cell tumors and malignant melanoma.

Applications
NSE is still a useful marker to identify peripheral nerves (Leonard et al, 1995). In the context of desmoplastic melanomas, which are often negative for the melanoma-specific markers HMB45 and NKIC3, NSE and S100 are sensitive markers (Anstey et al, 1994). However, when used for the identification of neuroendocrine differentiation, it is necessary that it be employed in a panel with more specific markers such as chromogranin, PHE 5 and synaptophysin. NSE positivity has been demonstrated in as many as 83% of testicular carcinoma in situ cases as well as in overt testicular germ cell tumors including seminomas, non-seminomas and mixed germ cell tumors (Kang et al, 1996).

Comments
Monoclonal antibodies to NSE produce less background staining, but specificity is only slightly increased. PGP 9.5 stains a very similar spectrum of cells and tumors. As PGP 9.5 shows greater sensitivity it would serve as a suitable substitute for NSE; however, neither marker should be used in isolation, especially when employed for the identification of neuroendocrine differentiation (Leong et al, 1989).

References
•Anstey A, Cerio R, Ramnarain N et al 1994. Desmoplastic malignant melanoma. An immunocytological study of 25 cases. American Journal of Dermatopathology; 16: 14-22.

•Bjerkehagen B, Fossa SD, Raabe N et al 1994. Transitional cell carcinoma of the renal pelvis and its expression of p53 protein, c-erbB-2 protein, neuron-specific enolase, Phe 5, chromogranin, laminin and collagen type IV. European Urology; 26: 334-339.

•Cooper EH 1994. Neuron-specific enolase. International Journal of Biological Markers 1994; 9: 205-210.

•Kang JL, Meyts ER, Skakkeback NE 1996. Immunoreactive neuronspecific enolase (NSE) is expressed in testicular carcinoma-in-situ. Journal of Pathology; 178: 161-165.

•Leonard N, Hourihane DO, Whelan A 1995. Neuroproliferation in the mucosa is a feature of coeliac disease and Crohn's disease. Gut; 37: 763-765.

•Leong AS-Y, Phillips GE, Pieterse AS 1986. Criteria for the diagnosis of primary endocrine carcinoma of the skin (Merkel cell carcinoma). A histological, immunohistochemical and ultrastructural study of 13 cases. Pathology; 18: 393-399.

•Leong AS-Y, Kan AE, Milios J 1989. Small round cell tumors in childhood: immunohistochemical studies in rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma and lymphoblastic lymphoma. Surgical Pathology; 2:5-17.

•Venores SA, Bonnin JM, Rubinstein LF 1984. Immunohistochemical demonstration of NSE in neoplasms of the CNS and other tissues. Archives of Pathology and Laboratory Medicine; 108: 536-540.

•Wick MR, Sheithauer BW, Kovacs E 1983. NSE in neuroendocrine tumors of the thymus, bronchus and skin. American Journal of Clinical Pathology; 29: 703-707.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.