S100 – Antibody Lexicon

Synonyms: S-100, S-100B

by Jan Klos

Background

S100 is Ca+ binding, 20 kDa highly acidic protein, engaged in forming of microtubules and cell growth. It consists of α- and β-units forming homo- or heterodimers. The protein is water soluble and resists long formalin fixation. The protein is essential for many cellular functions like diffusion across lipid membranes, assembly and stability of microtubules, activity and interaction of different enzymes.
It is important to remember that proteolytic pretreatment may result in false negative staining, while HIER usually enhances the results of positive staining.

Staining in normal cells

Positive staining seen in wide variety of normal cells and tissues: astrocytes, oligodendrocytes, ependymal cells, Schwann cells (ββ), melanocytes (αβ), endoneural cells, myoepithelial cells, Langerhans cells (ββ) and interdigitating reticulum cells, neurons, follicular dendritic cells (αα), fat cells, chondrocytes, some epithelial cells and tumors with these differentiations.

Staining in tumors

Variety of tumors differentiating in above directions are positive

90% of the cases: glioma, schwannoma, neurofibroma, melanocytic tumors (benign and malignant), granular cell tumor, myoepithelial tumors, polymorphous low grade adenocarcinoma of salivary glands, Langerhans cell histiocytosis, xanthogranuloma, chordoma, and most of benign and malignant lipomatous tumours.
The following express the protein in 50-90% of the cases: Primitive neuroectodermal tumours (neuroblastoma and others), malignant peripheral nerve sheath tumour, clear cell sarcoma, rhabdomyosarcoma, benign and malignant chondroid tumours, sweat gland carcinoma, serous and endometrioid carcinoma, renal cell carcinoma, papillary and follicular thyroid carcinoma, and acute monoblastic/monocytic leukaemia.
S-100 protein is found in 10-50% of the following: Granulosa cell tumour, Sertoli-Leydig cell tumours, alveolar soft part sarcoma, synovial sarcoma, Ewing sarcoma, vascular tumours, gastrointestinal stromal tumour, meningioma, adenocarcinomas of breast and gastrointestinal tract, carcinoids and other neuroendocrine tumours, anaplastic thyroid carcinoma.
The following rarely or never express S100: adenocarcinomas of the alimentary tract, lung, and prostate, transitional cell carcinoma, malignant mesothelioma, fibromatosis, fibrohistiocytic tumours, smooth muscle tumours, malignant lymphomas and germinal cell tumours.
In some tumours, the S-100 protein positivity is restricted to so-called sustentacular cells in phaeochromocytoma/paraganglioma, and some neuroendocrine tumors.
S-100 positive dendritic cells are particularly numerous in sclerosing variant of papillary carcinoma.

Staining pattern

Staining pattern is nuclear and cytoplasmic.

Control tissue

Appendix.

Application

Important antibody often recommended to use in panel and interpreted in context of staining with other antibodies.
Positive staining for S100 may indicate differentiation in chondroid, neural, melanocytic, myoepithelial, adipocytic and histiocytic lines including dendritic reticulum cells and Langerhans cells.
Benign nerve sheath tumors are always positive, but the malignant counterparts often show heterogeneous staining.
Only a small number (<5%) of melanomas most commonly in metastatic setting is negative. Frequency of positive staining in desmoplastic and neurotropic melanoma may be lower, but S100 staining is still very useful and sensitive marker in these cases.
Remember that a number of adenocarcinomas (thyroid, breast, lung, and ovary) and sex cord stromal tumors are also positive.
High frequency of S100 and CD34 combined positivity is not specific but is often reported in tumors with NTRK fusions – potential candidates for targeted therapy.

by Jan Klos

Background

Staining in normal cells

Staining in tumors

Staining pattern

Control tissue

Application

Selected references