S-100 protein as a marker for melanocytic and other tumours

The majority of melanocytic tumours are easily diagnosed but they become a problem when they are amelanotic and the tumour cells resemble those of other tumours. This applies particularly to secondary melanoma. Detection of S100 protein is a useful identifying marker. S100 protein, so named for its solubility in saturated ammonium sulphate, is derived from brain tissue. It is a dimer and belongs to a calcium binding group of proteins. The protein was first thought to be in neural or neural crest derived tissues but has been found in chondrocytes, adipocytes, myoepithelial cells, dendritic cells of lymphoid tissue, Langerhans cells and T lymphocytes. The protein is present in a high proportion of malignant melanomas and nevocytic nevi of skin, but is less positive in eye melanomas. It is present in gliomas, Schwannomas and neurofibromas but not in neurone derived tumours such as neuroblastomas. Chondromas, chondrosarcomas, liposarcomas, some osteogenic sarcomas and some histiocytic tumours are positive. The tumours that do not contain S100 protein are listed. Pending development of melanoma-directed monoclonal antibodies, the use of anti-serum to S100 protein plus anti-keratin and anti-leukocyte reagents is useful in the identification of tumours of doubtful histogenesis.     

S-100 protein: Is it useful as a tumour marker in diagnostic immunocytochemistry?

A heterogeneous group of 159 tumours was studied for the presence of S-100 protein by the immunoperoxidase technique in order to determine whether this marker may be of value in facilitating immunocytochemical diagnosis. Among cases of melanocytic and pigmented lesions, S-100 was widely distributed and demonstrated the strongest degrees of reactivity. S-100 protein was identified in virtually all nerve sheath tumours such as schwannomas, neurofibromas, myxoid sheath nerve tumour and also in some tumours of controversial histogenesis such as granular cell tumours. The great majority of carcinomas did not express S-100, with only two cases of breast carcinoma displaying focal S-100 staining. In a miscellaneous group of tumours S-100 was demonstrated in chordomas, myoepitheliomas and Wilms' tumour with Schwann cell differentiation. Despite its presence in a wide array of cell types, S-100 protein continues to be an extremely useful marker especially for soft tissue and peripheral nervous system tumours.     

S-100 protein is a differentiation marker in thyroid carcinoma of follicular cell origin: An immunohistochemical study

S-100 protein, a dimer of S-100α and S-100β subunits (S-100α and S-100β), is widely distributed in human tissue, and several papers describing S-100 protein expression in follicular cells of the thyroid have been published. in the present study, 105 cases of thyroid carcinoma (of which 96 were papillary, four follicular, two undifferentiated, and three meduilary) were analyzed immunohistochemically for the expression of S-100 protein, S-100α, S-100β, and thyroglobulin. in papillary carcinoma, 188 lesions were studled and classified into well differentiated types (56 papillary, 45 follicular) and poorly differentiated types (41 trabecular, four solid, eight squamoid, three tall, and one insular), because the histological structure of each tumor was heterogeneous. The percentage of lesions which expressed positively for 5–100 protein and S-100α, respectively, according to type were: papillary, 96 and 99%; foillcular, 96 and 100%; trabecular, 95 and 100%; solid, 50 and 50%; squamoid, 50 and 757%; and tall, 33 and 100%. The insular type was negative for both. For papillary carcinoma, well differentiated lesions showed stronger S-100α expression than poorly differentiated lesions. S-100α expression was weaker In follicular and undifferentiated carcinoma than in papillary carcinoma. Meduliary carcinoma also expressed S-100α. S-100β was positive in lesions that expressed S-100α strongly. Expression of S-100 protein and S-100α protein correlated with thyroglobulin synthesis in the follicular cells. It was concluded that S-100 protein, mainly S 100α. exists in thyroid follicular cells, that it exists In higher quantity in most of the well differentiated lesions but in lower quantity in poorly differentiated or Undifferentiated lesions, and that 5100 protein, especially S-100α, is a differentiation marker in carcinoma of thyroid follicular cell origin.     

Hypersensitivity to human brain S-100 protein in chronic alcoholics.

We have studied hypersensitivity to neurotissue in alcoholics. Fifty-four male chronic alcoholics with signs of mental deterioration, and 30 age-matched healthy male subjects were skin tested with human S-100 brain protein and liver protein, and protein purified derivate of tuberculin (PPD). The local Arthus and delayed sensitivity reactions were read at 4 hr and 24-48 hr respectively. Alcoholics and non-alcoholics exhibited a similar capacity to develop Arthus and delayed hypersensitivity to PPD. However, of all patients, 98.1% developed positive Arthus and 96.3% delayed skin reactions to S-100 protein, whereas 27.7% developed Arthus and 43.3% delayed reactions to liver protein. In non-alcoholics, the frequency of hypersensitivity reactions to S-100 protein and liver protein was low. The very high incidence of Arthus and delayed hypersensitivity reactions to a brain antigen in chronic alcoholics suggests that both humoral and cell-mediated immunity are involved in the pathogenesis of alcohol-induced brain damage.     

S-100 protein: a prognostic indicator in cutaneous malignant melanoma?

A series of 215 cases of cutaneous malignant melanoma referred to a single department of clinical oncology between 1940 and 1969 was studied to assess the accuracy of the Breslow thickness and the role of S-100 protein in predicting the clinical prognosis. Histological examination of these tumours showed that although the Breslow thickness correlated well with prognosis, in a significant number of cases it did not reliably forecast clinical outcome. From this series, tissue from those patients who survived disease-free for more than 10 years and those who died within a year of diagnosis was stained immunohistochemically for S-100 protein. Contrary to the findings of earlier studies, strong staining for S-100 protein was associated with improved survival (P less than 0.001). A marked increase in the incidence of cutaneous malignant melanoma was noted during the period of the study.     

Protein synthesis with special reference to S-100 protein in brain slices from rats receiving a restricted protein supply.

The synthesis of S-100 protein and that of soluble and total proteins was investigated using cerebral slices from rats fed a 20% or 3% protein containing diet for 6 days. Incorporation of radioactive amino acids into S-100 protein was significantly higher when rats were fed a diet containing 20% protein. No significant differences were obtained in the radioactivity incorporated into total or soluble proteins between the 2 dietary groups. 14C-leucine of aspecific radioactivity of 55 mCi/mmol or 3.2 mCi/mmol incorporated with time into total protein was similar for the 2 dietary groups. The time-dependent uptake of 14C-leucine by the slices and theinulin space remained unaffected by the dietary conditions used; and amino acid analyser estimates of the free amino acid pool showed no significant differences. Brain wet weight was 1.54+/-0.02 g and1.39+/-0.02 g for protein-fed and protein-restricted rats respectively. The corresponding body weight increased by 7.8 g/day or fell by 0.5 g/day. Although the differences observed in total protein synthesis were small the synthesis of a nervous tissue specific protein S-100 was markedly affected by short-term protein restriction.     

S-100 protein in white preadipocytes: an immunoelectronmicroscopic study

Differentiation of adipocytes from their precursor cells (preadipocytes) is an important problem in the study of the pathogenesis of obesity. Unfortunately, among the immature stages of adipocytes, only relatively differentiated forms can be identified by their fine structure; because early preadipocytes cannot be distinguished from fibroblasts solely on the basis of their morphology, it is impossible to assess the size of the preadipocyte population. S-100 protein has been identified in various mammalian tissues and recently mature adipocytes have been shown to be positive for this protein. Because fibroblasts are negative for S-100 protein, the present study tested the S-100 immunoreactivity of preadipocytes by the peroxidase-antiperoxidase (PAP) preembedding method at the ultrastructural level both in vivo and in culture. Mature adipocytes and early preadipocytes, including fibroblast-like cells devoid of lipid droplets, were positive both in vivo and in culture. Endothelial cells and pericytes were negative; but flattened, lipid-free, fibroblast-like cells surrounding the pericytes were positive. True fibroblasts both in vivo and in culture were negative. Therefore, S-100 protein can be a useful biochemical marker in distinguishing fibroblasts from early preadipocytes.     

S-100 protein in white preadipocytes: An lmmunoelectronmicroscopic study

Differentiation of adipocytes from their precursor cells (preadipocytes) is an important problem in the study of the pathogenesis of obesity. Unfortunately, among the immature stages of adipocytes, only relatively differentiated forms can be identified by their fine structure; because early preadipocytes cannot be distinguished from fibroblasts solely on the basis of their morphology, it is impossible to assess the size of the preadipocyte population. S-100 protein has been identified in various mammalian tissues and recently mature adipocytes have been shown to be positive for this protein. Because fibroblasts are negative for S-100 protein, the present study tested the S-100 immunoreactivity of preadipocytes by the peroxidase-antiperoxidase (PAP) preembedding method at the ultrastructural level both in vivo and in culture. Mature adipocytes and early preadipocytes, including fibroblast-like cells devoid of lipid droplets, were positive both in vivo and in culture. Endothelial cells and pericytes were negative; but flattened, lipid-free, fibroblast-like cells surrounding the pericytes were positive. True fibroblasts both in vivo and in culture were negative. Therefore, S-100 protein can be a useful biochemical marker in distinguishing fibroblasts from early preadipocytes.     

Absence of S-100 protein in prostatic glands

In eight cases of benign prostatic hyperplasia, two of which also contained well-differentiated prostatic adenocarcinoma, staining for S-100 protein was negative. These findings support the view that the outer layer of cells in prostatic acini is not myoepithelial in nature.     

The use of anti-idiotypic antibodies for the correction of autoimmune reactions to brain protein S-100

The possibility of eliminating hyperproduction of antibodies to brain protein S-100 in immunized mice through specific immunocorrection by anti-idiotypic antibodies to this protein or their Fab fragments is explored. Anti-idiotypic antibodies and their Fab fragments inhibit humoral immune response to S-100, which correlates with normalization of several behavior responses. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 11, pp. 508–511, November, 1996     

Cells which contain S-100 protein in Hodgkin''s disease: a quantitative study.

Paraffin sections from a series of 50 lymph nodes affected by Hodgkin's disease were examined by means of the unlabelled primary antibody peroxidase-antiperoxidase method to detect those cells which contained S-100 protein. In addition, 15 lymph nodes showing reactive follicular hyperplasia were studied. A simple enumeration procedure (eyepiece graticule) was used to count the number of such cells in 20 standard 25 X microscope fields. In the specimens of nodular sclerosing Hodgkin's disease many cells positive for S-100 protein were present, in contrast to the other Rye subtypes, which showed a relative paucity. By comparison, the lymph nodes showing reactive follicular hyperplasia contained a similar number of cells containing S-100 to those seen in the nodular sclerosing lymph nodes affected by Hodgkin's disease.     

Nocardia infections: clinical and biological aspects]

The nocardiosis is an infection caused by a bacterial pathogen agent, Nocardia, belonging to the Actinomycetales order. They are Gram-positive, strictly aerobic bacteria. Members of the genus Nocardia are ubiquitous. They are frequently isolated from soil, water, air dusts. The mode of contamination occurs by inhalation or by cutaneous or ocular traumatic lesion. Clinically, nocardiosis is essentially characterized by pulmonary diseases. Others secondary localizations are described, such as in the central nervous system. Nocardia can be responsible for important cutaneous, subcutaneous and lymphocutaneous manifestations. In the same way, some extrapulmonary diseases and spread nocardiosis are more rarely observed. Several factors seem to favour the development of Nocardia. The immunocompromised patients, particularly those with organ transplant and the patients treated with immunosuppressor treatments, offer strong predispositions to this opportunistic disease. The nocardiosis is nevertheless observed in healthy persons. In front of polymorphic and specific-less clinical manifestations, large phenotypic heterogeneity, and resistance profiles to specific antibiotics, a correct diagnosis for Nocardia species is necessary to apply an adequate treatment. The techniques of identification based on the chemotaxonomic analysis and the susceptibility to different inhibitors are efficient for the identification of genus and species. However, because of the slow growth rate of Nocardia, the reading of these tests can require several weeks of incubation. With the intention of the rapid identification of genus and species, the molecular techniques (PCR-RFLP) seem to be efficient. The technique of RAPD allows an efficient molecular typing, which will give a better knowledge concerning transmission, ecological niches and epidemic reservoirs.     

Expression of S-100 protein in renal cell neoplasms

Polyclonal antibody to S-100 protein has been routinely applied for initial screening of various types of tumors, including, melanocytic tumors and neurogenic tumors. S-100 protein has been shown to have a broad distribution in human tissues, including renal tubules. The potential utility of S-100 protein in renal cell neoplasms has not been extensively investigated. Using an EnVision-Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the diagnostic value of S-100 protein on tissue microarray sections from 175 cases of renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using the same antibody (anti-S-100 protein) was performed on 10 cases of renal cell neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and 13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100 protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%) of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of 30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in oncocytomas compared with ChRCCs was confirmed by the data of Western blot and cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3% (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (-)/S-100 protein (+). These data indicate that caution should be taken in interpreting an unknown primary with S-100 positivity and cytokeratin negativity. In addition, it suggests that S-100 has a diagnostic value in differentiating oncocytoma from ChRCC.     

Effect of the S-100 protein on the RNA-polymerase activity in brain nucleoli isolated from newborn rat

The structural integrity of the nucleus is not a prerequisite for the action of the S-100 protein on the RNA-polymerase activity in brain nuclei. In fact the protein also stimulates the enzyme activity in sonicated nuclei of newborn rat, as well as directly in isolated nucleoli from the same source.