S-100

This is a dimeric acidic calcium-binding protein.  It was first isolated from the central nervous system. It is a dimer with alpha and beta subunits, able to combine in three isoforms S-100ao (alpha dimer), S-100a (alpha-beta isoform) and S-100b (beta dimer). There are structural similarities to the calcium-binding domain of calmodulin. It is a calcium flux regulator. The name derives from its solubility in 100% saturated ammonium sulphate.

It has more recently become apparent that there is a whole family of related calcium binding proteins.

Polyclonal and monoclonal antibodies are available. Some of the monoclonal antibodies are specific to alpha or betas subunits and so have a more limited range of immunoreactivity than do the polyclonal antibodies.

Immunohistochemical expression

S-100 is present in the nucleus and cytoplasm of:

• glial and Schwann cells (preferentially labelled by monoclonal antibodies to the beta subunit²)

• Pacinian corpuscles

• melanocytes, naevus cells and melanomas

• amelanotic cellular blue nevus: 7/8³

• chondrocytes

• notochord and chordoma

• adipocytes, lipomas and liposarcomas

• myoepithelial cells

• skin adnexal tumours

• breast tumours

• salivary gland tumours

• sustentacular cells of adrenal medulla and paraganglia

• interdigitating reticulum cells of the paracortex of lymph nodes

• dendritic reticulum cells of lymphoid follicles

• Langerhans' cells

It is expressed by the tumours derived from the above cells:

• 50% of malignant peripheral nerve sheath tumours stain for S-100

• benign and malignant granular cell tumours

• 50% of granulosa cell tumours stain for S-100. 

• carcinoid tumours:

foregut	7/171
midgut	6/121
hindgut	5/101

sustentacular cells also stain positively in carcinoids of foregut and midgut but not hindgut¹

Diagnostic utility

The diagnostic value is limited by the widespread expression of S-100. 

• It is useful in the diagnosis of melanoma.  It is more commonly expressed in metastatic melanomas than is HMB-45.

• differentiation of cartilaginous tumours from other bone tumours

• differentiation of sclerosing adenosis (where myoepithelial cells are positive) from tubular carcinoma of the breast

• differentiation of Paget's disease from superficial spreading melanoma

References

¹Al-Khafaji et al. Immunohistologic analysis of gastrointestinal and pulmonary carcinoid tumours. Human Pathol 1998;29:992-9.

²Diagnostic Immunohistochemistry edited by Professor D. J. Dabbs, page 70

³Zembowicz, A., S. R. Granter, et al. (2002). "Amelanotic cellular blue nevus: a hypopigmented variant of the cellular blue nevus: clinicopathologic analysis of 20 cases." Am J Surg Pathol 26(11): 1493-1500.

This page last revised 21.12.2001.

©SMUHT/PW Bishop