Synaptophysin (SYP)

Characteristics

SYP is a calcium binding integral-membrane glycoprotein, 38 kDa of presynaptic vesicles in all neurons (Fig. 1A)and corresponding vesicles in all neuroendocrine (NE) cells (Fig. 1B). Moreover SYP is detected in choroid plexus epithelium. Staining is also seen in adrenal cortical cells, goblet cells and Paneth cells, probably due to a closely related protein.

Neoplasms

SYP is detected in virtually all neuronal tumours: Neuroblastoma, ganglioneuroblastoma, ganglioneuroma, ganglioglioma, central neurocytoma, and phaeochromocytoma/paraganglioma. SYP may also be detected in other neural crest derived tumours like oligodendroglioma, astrocytoma (Fig. 2A) and ependymoma, however, to a varying extend. Moreover synaptophysin is detected in NE tumours like pancreatic islet tumours, carcinoid (Fig. 2B) and neuroendocrine carcinoma, small cell carcinoma, medullary thyroid carcinoma (Fig. 2C), and pituitary and parathyroid adenomas.

Also adrenal cortical tumours stain for synaptophysin (Fig. 2D).

Application

SYP is a sensitive marker for the identification of neuronal and NE tumours and NE differentiation. However, it is not as specific as chromogranin A.  SYP may also be used for the identification of adrenal cortical tumour.

Visualization

The staining product should be granular cytoplasmic. mAbs clone 27G12 and clone Snp88 are useful Abs. Also several pAbs are available (we have obtained good results with pAb A0010 from Dako). A slight nuclear staining with clone snp88 may be seen, but without interference with the interpretation. mAb clone SY38, which is the oldest on the market, has been widely used. However, in our experience, the signal-to-noise ratio is poor with SY38 compared to newer Abs.

Heat induced epitope retrieval (HIER) is mandatory with most antibodies (including both mAb clones 27G12, Snp88 and SP11 and pAb A0010 from Dako). A high pH buffer is preferable. Non-specific staining is rare but false negative staining reactions due to insensitive protocols are frequent. Control: Normal appendix: The axons of the nerves in the muscularis propria must show a strong distinct granular reaction while the surrounding muscle cells being negative (photo).   Assessments Run 5 2002 Run 18 2006 Run 22 2008 Run 29 2010 Run 37 2013

Selected references

Erickson LA, Lloyd RV. Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol. 2004 Jul;11(4):175-89.

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

Portela-Gomes GM, Hacker GW, Weitgasser R. Neuroendocrine cell markers for pancreatic islets and tumors.
Appl Immunohistochem Mol Morphol. 2004 Sep;12(3):183-92.

Wick MR. Immunohistology of neuroendocrine and neuroectodermal tumors. Semin Diagn Pathol. 2000 Aug;17(3):194-203.