Sources/Clones
Accurate (polyclonal), Biodesign (polyclonal), Biogenesis (15E2E2, polyclonal), Biogenex (15E2E2, polyclonal), Chemicon (monoclonal, polyclonal), Cymbus Bioscience (MIG5), Dako (polyclonal), ICN (polyclonal), Immunotech (polyclonal), Medac (S1/61/69), Novocastra (polyclonal), Oncogene (OS94.5), RDI (MIG-5), Seralab (polyclonal), Serotec (polyclonal), Sigma (polyclonal) and Zymed (polyclonal).
Fixation/Preparation
Formalin-fixed tissues are ideally suited for S100 immunostaining and the antigen is resistant to long durations of fixation in formalin. Its reactivity can still be enhanced by heat-induced antigen retrieval but not by proteolytic digestion.
Background
S100 protein, so named because of its solubility in a saturated ammonium sulfate solution, occurs as three biochemically distinct forms. Each is a protein dimer of two subunits, designateda and b. The three dimers are S100A (a-b), S100A (a-b), and S100B (b-b). The a and b subunits each have a molecular weight of approximately 10.5 kD with extensive amino acid sequence homology between the two subunits. They both have amino acid sequences known to code for the calcium-binding sites of the calmodulin family of proteins. S100 is highly acidic and water soluble with varying affinities for calcium, zinc and manganese. These properties are related to many basic cell functions such as cation diffusion across lipid membranes, microtubule assembly and stability, calcium and cyclic nucleotide regulation and increased activity of RNA polymerase, drug-protein interactions, the plasma membrane function of neurons and interaction with chromosomes and synaptosomes. S100 protein is conserved in nature and is present within the cells of all three germ layers in humans, a reflection of its important role in basic cell function.
Applications
S100 has been demonstrated in a wide variety of normal and abnormal tissues. Formalin fixation and paraffin embedding may alter antigenic sites and aldehyde fixation may prevent diffusion of the highly soluble antigen that can produce artefactual immunolocalization patterns. Indeed, one study has reported granular staining of virtually every cell type when fresh-frozen tissue was stained with a monoclonal S100 antibody.
Normal and neoplastic cartilaginous tissue, including benign and malignant chondroid tumors, express S100 protein and this is useful for the distinction of non-cartilaginous bone tumors which are mostly negative for the antigen. Cartilaginous tumors can be distinguished from chordomas by the presence of cytokeratin and EMA in the latter and their absence in the former. S100 is also useful for the labeling of myoepithelial cells in mammary ducts, particularly when distinguishing sclerosing adenosis from tubular carcinomas, the former displaying a distinct layer of myoepithelial cells. Sustentacular or satellite cells of the adrenal medulla and paraganglia and their corresponding tumors are labeled by S100 antibodies, as are the folliculostellate cells of the anterior pituitary (Nakajima et al, 1982; Takahashi et al, 1984; Loeffel et al, 1985).
The S100 antigen is a useful marker of peripheral nerve cells. The protein is present in the nuclei and cytoplasm of Schwann cells and satellite cells in parasympathetic and sympathetic ganglia (Daimaru et al, 1985). Theb-subunit has been reported in these cells but not in neurons, the latter contain the a-subunit that is not expressed in Schwann cells or satellite cells. Pacinian corpuscles also contain S100 protein. While S100 protein is expressed in the majority of benign nerve sheath tumors, as many as 40-50% of malignant Schwann cells do not stain. A population of S100+ Schwann cells can be demonstrated in neurofibromas but variable numbers of perineural and intermediate cells within these tumors do not stain for S100 protein. Correspondingly, neurogenic sarcomas arising in patients with neurofibromatosis show a spectrum of expression of S100 protein. Both benign and malignant granular cell tumors contain S100 protein expressed as theb-subunit, a feature used to support an origin from Schwann cells.
The other group of cells which are labeled by S100 antibodies are the histiocytes. The interdigitating reticulum cells of the paracortical areas in the lymph node are stained by S100 protein antibodies, as are dendritic reticulum cells of the lymphoid follicles. Langerhans' cells of the skin, mucous membranes and other sites are also positive for S100 protein, expressing S100B activity (b-b). As such, S100 protein is a useful marker for the identification of Langerhans' cell histiocytosis.
One of the most useful applications of the S100 protein is as a marker of nevus cells and melanomas. Virtually all benign melanocytic lesions contain S100 protein which is also observed in over 95% of malignant melanomas. When used in conjunction with a panel comprising cytokeratin, vimentin and LCA, it allows the distinction of malignant melanoma from its common mimics, namely, anaplastic carcinoma and large cell lymphoma. Similarly, the inclusion of anti-CEA forms a useful panel to distinguish Bowens' disease, Pagets' disease of the skin and superficial spreading malignant melanoma. Because a small number of melanomas may fail to express S100 protein, antibodies to HMB-45 and the melanoma-associated antigen NKI/C3 are useful additional markers for melanoma.
S100 protein is expressed by adipocytes and a proportion of liposarcomas also stain positive. Tumors of the cutaneous adnexae and salivary glands also express S100 protein.
Comments
Although S100 protein is a useful marker for the identification of melanoma, Langerhans' cell histiocytosis and peripheral nerve tumor, the antibodies should be used in the context of the differential diagnosis derived from morphologic and clinical appearances. A wide variety of carcinomas, including those from the lung, pancreas and female genitourinary tract, as well asMycobacteria ulcerans organisms have been reported to show positivity so that S100 antibodies should not be used or interpreted in isolation. We have also observed the staining of be ign skeletal and smooth muscle cells with some anti-S100 antibodies.
References
•Daimaru Y, Hashimoto H, Enjoji M 1985. Malignant peripheral nerve sheath tumours (malignant schwannomas). An immunohistochemical study of 29 cases. American Journal of Surgical Pathology 9: 434-444.
•Loeffel SC, Gillespie GY, Mirmiran SA et al 1985. Cellular immunolocalisation of S100 protein within fixed tissue sections by monoclonal antibodies. Archives of Pathology and Laboratory Medicine 109: 117-122.
•Nakajima T, Watanabe S, Sato Y et al 1982. An immunoperoxidase study of S100 protein distribution in normal and neoplastic tissues. American Journal of Surgical Pathology 6: 715-727.
•Takahashi K, Isobe T, Ohtsuki Y et al 1984. Immunohistochemical study on the distribution ofa and b subunits of S100 protein in human neoplasm and normal tissues. Virchow's Archives Cellular Pathology 45: 385.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Accurate (polyclonal), Biodesign (polyclonal), Biogenesis (15E2E2, polyclonal), Biogenex (15E2E2, polyclonal), Chemicon (monoclonal, polyclonal), Cymbus Bioscience (MIG5), Dako (polyclonal), ICN (polyclonal), Immunotech (polyclonal), Medac (S1/61/69), Novocastra (polyclonal), Oncogene (OS94.5), RDI (MIG-5), Seralab (polyclonal), Serotec (polyclonal), Sigma (polyclonal) and Zymed (polyclonal).
Fixation/Preparation
Formalin-fixed tissues are ideally suited for S100 immunostaining and the antigen is resistant to long durations of fixation in formalin. Its reactivity can still be enhanced by heat-induced antigen retrieval but not by proteolytic digestion.
Background
S100 protein, so named because of its solubility in a saturated ammonium sulfate solution, occurs as three biochemically distinct forms. Each is a protein dimer of two subunits, designateda and b. The three dimers are S100A (a-b), S100A (a-b), and S100B (b-b). The a and b subunits each have a molecular weight of approximately 10.5 kD with extensive amino acid sequence homology between the two subunits. They both have amino acid sequences known to code for the calcium-binding sites of the calmodulin family of proteins. S100 is highly acidic and water soluble with varying affinities for calcium, zinc and manganese. These properties are related to many basic cell functions such as cation diffusion across lipid membranes, microtubule assembly and stability, calcium and cyclic nucleotide regulation and increased activity of RNA polymerase, drug-protein interactions, the plasma membrane function of neurons and interaction with chromosomes and synaptosomes. S100 protein is conserved in nature and is present within the cells of all three germ layers in humans, a reflection of its important role in basic cell function.
Applications
S100 has been demonstrated in a wide variety of normal and abnormal tissues. Formalin fixation and paraffin embedding may alter antigenic sites and aldehyde fixation may prevent diffusion of the highly soluble antigen that can produce artefactual immunolocalization patterns. Indeed, one study has reported granular staining of virtually every cell type when fresh-frozen tissue was stained with a monoclonal S100 antibody.
Normal and neoplastic cartilaginous tissue, including benign and malignant chondroid tumors, express S100 protein and this is useful for the distinction of non-cartilaginous bone tumors which are mostly negative for the antigen. Cartilaginous tumors can be distinguished from chordomas by the presence of cytokeratin and EMA in the latter and their absence in the former. S100 is also useful for the labeling of myoepithelial cells in mammary ducts, particularly when distinguishing sclerosing adenosis from tubular carcinomas, the former displaying a distinct layer of myoepithelial cells. Sustentacular or satellite cells of the adrenal medulla and paraganglia and their corresponding tumors are labeled by S100 antibodies, as are the folliculostellate cells of the anterior pituitary (Nakajima et al, 1982; Takahashi et al, 1984; Loeffel et al, 1985).
The S100 antigen is a useful marker of peripheral nerve cells. The protein is present in the nuclei and cytoplasm of Schwann cells and satellite cells in parasympathetic and sympathetic ganglia (Daimaru et al, 1985). Theb-subunit has been reported in these cells but not in neurons, the latter contain the a-subunit that is not expressed in Schwann cells or satellite cells. Pacinian corpuscles also contain S100 protein. While S100 protein is expressed in the majority of benign nerve sheath tumors, as many as 40-50% of malignant Schwann cells do not stain. A population of S100+ Schwann cells can be demonstrated in neurofibromas but variable numbers of perineural and intermediate cells within these tumors do not stain for S100 protein. Correspondingly, neurogenic sarcomas arising in patients with neurofibromatosis show a spectrum of expression of S100 protein. Both benign and malignant granular cell tumors contain S100 protein expressed as theb-subunit, a feature used to support an origin from Schwann cells.
The other group of cells which are labeled by S100 antibodies are the histiocytes. The interdigitating reticulum cells of the paracortical areas in the lymph node are stained by S100 protein antibodies, as are dendritic reticulum cells of the lymphoid follicles. Langerhans' cells of the skin, mucous membranes and other sites are also positive for S100 protein, expressing S100B activity (b-b). As such, S100 protein is a useful marker for the identification of Langerhans' cell histiocytosis.
One of the most useful applications of the S100 protein is as a marker of nevus cells and melanomas. Virtually all benign melanocytic lesions contain S100 protein which is also observed in over 95% of malignant melanomas. When used in conjunction with a panel comprising cytokeratin, vimentin and LCA, it allows the distinction of malignant melanoma from its common mimics, namely, anaplastic carcinoma and large cell lymphoma. Similarly, the inclusion of anti-CEA forms a useful panel to distinguish Bowens' disease, Pagets' disease of the skin and superficial spreading malignant melanoma. Because a small number of melanomas may fail to express S100 protein, antibodies to HMB-45 and the melanoma-associated antigen NKI/C3 are useful additional markers for melanoma.
S100 protein is expressed by adipocytes and a proportion of liposarcomas also stain positive. Tumors of the cutaneous adnexae and salivary glands also express S100 protein.
Comments
Although S100 protein is a useful marker for the identification of melanoma, Langerhans' cell histiocytosis and peripheral nerve tumor, the antibodies should be used in the context of the differential diagnosis derived from morphologic and clinical appearances. A wide variety of carcinomas, including those from the lung, pancreas and female genitourinary tract, as well asMycobacteria ulcerans organisms have been reported to show positivity so that S100 antibodies should not be used or interpreted in isolation. We have also observed the staining of be ign skeletal and smooth muscle cells with some anti-S100 antibodies.
References
•Daimaru Y, Hashimoto H, Enjoji M 1985. Malignant peripheral nerve sheath tumours (malignant schwannomas). An immunohistochemical study of 29 cases. American Journal of Surgical Pathology 9: 434-444.
•Loeffel SC, Gillespie GY, Mirmiran SA et al 1985. Cellular immunolocalisation of S100 protein within fixed tissue sections by monoclonal antibodies. Archives of Pathology and Laboratory Medicine 109: 117-122.
•Nakajima T, Watanabe S, Sato Y et al 1982. An immunoperoxidase study of S100 protein distribution in normal and neoplastic tissues. American Journal of Surgical Pathology 6: 715-727.
•Takahashi K, Isobe T, Ohtsuki Y et al 1984. Immunohistochemical study on the distribution ofa and b subunits of S100 protein in human neoplasm and normal tissues. Virchow's Archives Cellular Pathology 45: 385.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
