Neurofilament protein (NFP)

Characteristics

NFP is a class 4 intermediate filament protein comprising three heteropolymeric polypeptide units, 70 kda, 160 kda and 200 kDa. NFP is represented in virtually all neurons. The filaments in the perikarya are mostly unphosphorylated while increasing phosphorylation (which is needed for the polymerization) occurs as the filaments move along the axons (Fig. 1A-B). Among (neuro-)endocrine cell, NFP (mainly unphosphorylated) is found in adrenal phaeochomocytes and zona glomerulosa cells, and pancreatic islet cells and may also appear in other endocrine cells (appropriate studies are lacking!).

Neoplasms

NFP, particularly unphosphorylated filaments, can be demonstrated in the large majority of differentiated neuronal tumours: ganglioneuroma, ganglioneuroblastoma, etc., in some cases of primitive neuroectodermal tumour (neuroblastoma etc., Fig. 2A-B), phaeochromocytoma/paraganglioma, and neuroendocrine tumours like medullary thyroid carcinoma, carcinoid, Merkel cell carcinoma, and small cell carcinoma. Also unphosporylated NFP may be detected in neural crest tumours like astrocytoma, meningioma (Fig. 2C), and malignant melanoma. The proportions of tumour and tumour cells are, however, highly dependent on the antibody (see Visualization).

In neurofibroma, disperse phosporylated NFP positive axons are found between the other cell components, which are NFP negative (Fig. 2D).

Application

Demonstration of phosphorylated NFP is useful for identification of nerve structures, e.g., in neurofibroma, and the visualization of nerve swelling in axonal damage. Antibodies to unphosphorylated  NFP may be included in a panel for classification of intracranial tumours: identification of neuronal tumours and of neuronal differentiation in primitive tumours. However, the use is limited because of the varying reactivity depending on the antibody specificity.

Visualization

Antibodies to neurofilament proteins, which are independent of phosporylation, e.g., clone N52 against the 200 kDa filament, stain a large proportion of neural crest tumours, while antibodies, which only reacts with phosphorylated types, e.g., clone 2F11 against the 70 kDa filament, have a limited reaction profile, primarily decorating differentiated neurons (perikarya and particularly axons). The mAb cocktail NFP7/DA2/RMd020.11 is a pan-NFP-antibody with a staining pattern resembling that of clone N52, but the reactivity in various neuronal tumours is only partly overlapping, making it advisable to use the two Abs in tandem.

Heat induced epitope retrieval (HIER) in an alkaline buffer is recommended for the Abs mentioned above.

Control tissue: Appendix: the ganglion cells and axons in the muscularis propria should show the strongest possible reaction without obtaining false positive reaction of other cells (enterocytes, lymphocytes, smooth muscle cells).

Assessments

Run 18 2006

Selected references

Gotow T. Neurofilaments in health and disease. Med Electron Microsc. 2000;33(4):173-99.

Morrison CD, Prayson RA. Immunohistochemistry in the diagnosis of neoplasms of the central nervous
system. Semin Diagn Pathol. 2000 Aug;17(3):204-15.

Petzold A. Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration
and loss. J Neurol Sci. 2005 Jun 15;233(1-2):183-98.