Immunocytochemistry of paragangliomas—value of staining for S-100 protein and glial fibrillary acid protein in diagnosis and prognosis

Surgical specimens of 65 adrenal and 27 extra-adrenal paragangliomas, the latter comprising 11 carotid body, five jugulotympanic, one aorticopulmonary, eight aorticosympathetic and two visceral autonomic tumours, were examined immunocytochemically for the presence of glial fibrillary acid protein (GFAP) and S-100 protein. Six adrenal and four extra-adrenal (one parasympathetic and three sympathetic) neoplasms pursued a malignant clinical course. S-100 staining of sustentacular (type 2) cells was seen in both adrenal (48/65) and extra-adrenal (23/27) lesions, the 10 malignant tumours being entirely devoid of S-100 protein positive cells. GFAP positivity of type 2 cells was seen in only 16 of the extra-adrenal tumours, all of these lesions belonging to the group of benign parasympathetic paragangliomas. The presence of S-100 positive type 2 cells may thus help to exclude malignancy in individual paraganglioma cases, while GFAP positivity of such cells renders possible the correct typing of benign parasympathetic paragangliomas.     

Immunohistochemical distribution of S-100 protein and glial fibrillary acidic protein in normal and neoplastic salivary glands

Summary Immunohistochemical localization of S-100 protein, its and subunits, and glial fibrillary acidic protein (GFAP) in normal and neoplastic salivary glands was studied by the peroxidase-antiperoxidase method and immunoblot analysis. Positive immunostaining for S-100 protein was observed in pleomorphic adenoma, adenolymphoma, tubular adenoma, adenoid cystic carcinoma, acinic cell tumour, adenocarcinoma and carcinoma in pleomorphic adenoma. S-100 protein was localized in myoepithelial cells, epithelial cells of intercalated ducts and serous acinar cells of normal salivary gland. Both and subunits of S-100 protein showed almost identical distribution in normal and neoplastic salivary glands, but skeletal muscle cells were -positive/-negative whereas Schwann cells and fat cells were -negative/-positive in the stroma and neighbouring tissue. GFAP was only found in pleomorphic adenoma and its malignant counterpart. Immunoblot analysis showed that the GFAP-related antigen consisted of several polypeptide bands with a molecular weight ranging between 35,000 to 50,000 daltons.     

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.     

胚胎小肠S-100+树突状细胞的组织分布

目的：观察人胚胎小肠树突状细胞(dendritic cells,DCs)的组织分布。方法：应用SABC免疫组织化学法对人胚胎小肠DC的出现时间、分布部位、形态以及数量等进行研究。结果：(1)人胚胎小肠各段S-100^ DC于第9～11W相继出现,主要分布于粘膜固有层,外形不规则,第24W以后,其突起相连逐渐在固有层形成网状结构。(2)回肠集合淋巴小结S-100^ DC以滤泡问区数量最多,其外形相对规则。结论：人胚胎小肠S-100^ DC主要分布于固有层,其数量随胎龄的增加而逐渐增加,而回肠集合淋巴小结S-100DC呈区域性分布,它们与固有层S-DC在形状、大小和数量上有所不同。     

Immunocytochemical localization of S-100 protein in interstitial cells of the monkey Macaca irus pineal gland

Pineal interstitial cells of the monkey Macaca irus were shown to react with an anti-human S-100 protein antibody, using the indirect immunoperoxidase technique on sections of paraplast-embedded pineal glands. Immunoreactivity was seen in the cytoplasm of the cells, stellate in shape and intermingled with pinealocytes; the latter did not stain with the antiserum against S-100 protein. Immunoreactivity was also present in the nuclei, as was reported in various other cell types immunostained with anti-S-100 protein antibodies. The present results support the view that interstitial cells of the monkey Macaca irus pineal gland may be of astroglial origin.     

S-100 protein positive cells in nasopharyngeal carcinoma (NPC): Absence of prognostic significance

Summary An immunohistochemical study of S-100 protein in 43 nasopharyngeal carcinomas (NPC) of known clinical evolution (33 primary and 10 metastatic) is presented. Sixty per cent of primary site cases as well as all metastatic forms showed S-100 protein positive cells intermingled with tumour cells. These S-100 positive elements were identified as Langerhans cells. No significant differences were found when correlating S-100 protein positivity and histological NPC variants, neither in age nor in sex of patients. Statistical analysis failed to demonstrate any positive correlation between S-100 protein reactivity and clinical survival.     

Immunohistochemical study of neuron specific enolase and S-100 protein in Hirschsprung's disease

Summary The distribution of whole differentiated neurons in the intestines from 15 children with Hirschsprung's disease was investigated using neuron specific enolase (NSE) and the perineuronal elements were studied using S-100 protein immunostaining.In aganglionic segments, NSE immunoreactive ganglion cells and S-100 positive satellite cells were absent, but the hypertrophic nerve trunks did show a markedly positive NSE and S-100 immunoreactivity.Two different forms of aganglionic segment were present. One was the middle aganglionic segment of long segment aganglionosis which was almost completely dennervated. In the other type, there were several NSE positive nerve fibers in the muscularis propria of both the aganglionic segment of short segment aganglionosis and the distal aganglionic segment of long segment aganglionosis. These latter two aganglionic segments seemed to be innervated by extrinsic nerves.     

Localization of S-100 protein in a Leydig and Sertoli cell tumour of testis

A Sertoli-Leydig cell tumour of testis presented some diagnostic difficulties. The tumour cells showed strong expression of S-100 antigen. Preliminary study of non-neoplastic testis suggests that Leydig cells and, to a lesser extent, Sertoli cells express S-100 antigen; its localization may be of value in the diagnosis of sex cord-stromal tumours of testis.     

Glial fibrillary acidic protein in medulloblastomas and other embryonic CNS tumours of children

Summary Investigation of GFAP in 50 medulloblastomas showed a few GFAP-positive tumour cells in 5 cases only; 17 tumours were negative, and 28 showed a pseudopositivity, i.e. GFAP-bearing cells were identified as reactive or degenerating astrocytes, intermingled with tumour elements. A high GFAP content was seen in 2 small-cell gliomas of the cerebellum, whereas 3 pineoblastomas, 2 neuroblastomas of CNS, and one medulloepithelioma were negative.GFAP is a very good method for identificating astrocytes, but does not seem to be reliable for identifying the origin of undifferentiated tumours such as medulloblastomas. In these neoplasms glial differentiation is lacking or extremely rare, GFAP-positivity being mostly an artifact. The investigation of small tumour samples or the positivity of a single cell are inadequate data for a correct evaluation of the findings, especially taking in mind that GFAP of degenerated astrocytes can be phagocytised by cells other than glial (e.g., macrophages, epithelial and meningioma cells). The importance of carefully checking the whole structure of the tumour is stressed, GFAP positivity or negativity being not a sufficient criterion for its nosological classification.     

Glial fibrillary acidic protein immunoreactivity in the rat suprachiasmatic nucleus: circadian changes and their seasonal dependence

The pacemaker of the biological clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, was studied in intact male rats to determine its immunoreactivity to glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Animals were kept under 12-h light-dark cycles in synchrony with day-night periods. Immunohistochemical reactions were carried out at midday and late at night in both winter (January) and summer (July). In winter, GFAP immunoreactivity was found to be low during the day and high at night. The findings were reversed in summer, when GFAP immunoreactivity was high during the day and low at night. Increased GFAP immunoreactivity appeared in the form of an abundance of thick immunopositive fibres rather than of cell bodies. This was interpreted as a hypertrophy of pre-existing astrocytes due to alternating photic stimulation conveyed by retinofugal fibres to the SCN. The observed seasonal reversal in the direction of GFAP oscillations raises the possibility that a circannual timer exists outside the SCN.     

S-100 protein immunostaining in cells of dendritic morphology within reactive germinal centers by ABC immunoperoxidase method

Summary The dendritic and the interdigitating (IRC) reticulum cells are commonly reported to have different topographical distribution in the human lymphoid tissue and some peculiar cytochemical and immunohistochemical features. These include the detection of S-100 protein by PAP (peroxidase anti-peroxidase) method only in IRC located in the thymus-dependent areas. In 15 reactive lymphoid tissue specimens (11 lymph nodes, 3 tonsils, and 1 adenoid) the presence of S-100 protein was tested by ABC (avidin-biotin complex) immunoperoxidase method. IRC were constantly positive. Other positive cells were located within the follicular germinal centers; these immunostained cells appeared as a striking network composed of dendritic-shaped processes displaying a finely granular positivity for S-100 protein. It is suggested that by using this very sensitive technique, S-100 protein can also be detected in intrafollicular cells of dendritic morphology.This study was in part supported by Grant n.84.00525.44 from Consiglio Nazionale delle Ricerche Progetto Finalizzato Oncologia Roma     

Glial fibrillary acidic protein (GFAP)-like immunoreactivity in normal and transected rat olfactory nerve

Summary Normal and transected rat olfactory nerves were stained immunohistochemically using a monoclonal antibody previously shown to selectively detect GFAP-like immunoreactivity in central astrocytes but not in peripheral Schwann cells. Low levels of central type GFAP were found in the olfactory nerves, presumably in ensheathing cells. The levels of GFAP increased dramatically after nerve transection. A population of strongly GFAP-positive cells was detected at the junction between the olfactory epithelium and initial part of the nerves, of possible relevance to the regenerative abilities of this pathway.     

Immunohistochemical demonstration of S-100 protein in salivary gland neoplasms

A peroxidase-antiperoxidase technique for S-100 protein has been applied to 68 salivary glands. These included 17 pleomorphic adenomas, seven adenoid cystic carcinomas, 23 adenolymphomas and a number of other neoplasms. In addition, five specimens of myoepithelial sialadenitis ('benign lymphoepithelial lesion') and five normal parotid glands were included. Consistent results were obtained, myoepithelial cells and cells in myxoid and chondroid areas in pleomorphic adenomas staining intensely. In adenoid cystic carcinoma, on the other hand, there was no staining. The adenolymphomas possessed intensely S-100 protein-positive cells in the interfollicular lymphoid areas; these were probably interdigitating reticulum cells. In addition, branching structures, probably corresponding to Langerhans' cells, were observed in the epithelium of adenolymphomas.     

Glial fibrillary acidic protein immunoreactivity in normal and diseased human breast

Summary Immunostaining for glial fibrillary acidic protein (GFAP) identifies a minor subpopulation of immunoreactive myoepithelial cells in the normal resting human breast. The GFAP-immunoreactive cells also express a panel of myoepithelial cell markers, including cytokeratin 14 (CK 14), vimentin, smooth-muscle-specific actin isoforms, nerve growth factor receptor (NGFR) and common acute lymphoblastic leukaemia antigen (CALLA). The percentage of GFAP-immunoreactive myoepithelial cells is greatly increased in various neoplastic and non-neoplastic diseases of the breast, being highest in adenomyoepitheliomas. Furthermore, in all the instances of fibroadenoma, phyllodes tumour, epitheliosis and gynaecomastia, a variable number of epithelial cells also acquires immunoreactivity for GFAP, vimentin, CK 14, NGFR and, to a lesser extent, for CALLA. Conversely, GFAP immunoreactivity has never been encountered in the malignant cells of the different types of breast carcinoma. These findings suggest that the expression of GFAP might be a (possibly transient) feature of proliferating epithelial and myoepithelial cells in breast diseases other than carcinomas.     

Immunohistochemical studies on S-100 cells in the anterior pituitary gland of Sprague Dawley rats and spontaneous dwarf rats

The S-100 cells in the pituitary glands of adult male Sprague Dawley rats (SDs) and spontaneous dwarf rats (SDRs) were immunohistochemically examined using anti-S-100 and anti-S-100 monoclonal antibodies. The immunoreactive cells against S-100 protein were divided into three subtypes on the basis of their immunore-activity against subunits of S-100 protein: S-100 dominant type (the -type cell), S-100 dominant type (the \-type cell) and immunoreactive against both S-100 and S-100 (the -type cell). In the SD, -type cells represented 26% of the total S-100 immunoreactive cells (S-100 cells) and were localized in the peripheral area of the ventral region of the pituitary gland. This type of cell was observed forming clusters, with more abundant cytoplasm than the -type cell. The proportion of -type cells was 53%. They were diffusely distributed throughout the gland, and their processes were thicker than those of the -type cell. In the SDR, the proportion of -type cells was 55%, and they were observed throughout the gland. In contrast, -type cells totalled 12% and were localized in small areas of the central and peripheral region of the gland. The proportion of -type cells was 21% in the SD and 33% in the SDR and they were observed forming small clusters in both animal groups. The proportion of -type cells compared with the total of S-100-immunoreactive cells was significantly higher (P < 0.05) in the SDR than in the SD, while the proportion of -type cells was markedly lower (P < 0.05).     

B16黑色素瘤组织中上皮型钙黏附分子和S-100蛋白的表达及意义

目的:探讨B16黑色素瘤小鼠体内上皮型钙黏附分子与S-100蛋白的表达在肿瘤侵袭及转移过程中发挥的作用。方法:C57纯系小鼠分为12d和25d肿瘤组和正常对照组。肿瘤组将B16黑色素瘤细胞人工植入C57小鼠背部皮下,制荷瘤鼠模型,免疫组织化学法检测肿瘤病变中心区及交界区皮肤上皮型钙黏附分子和S-100的表达。结果:12d肿瘤组肿瘤组织中S-100蛋白表达的面密度和数密度明显增高,与正常对照组和25d肿瘤组比较差异有统计学意义;肿瘤组织中上皮型钙黏附分子表达的面密度和数密度较正常对照组明显降低。结论:上皮型钙黏附分子和S-100蛋白的异常表达在皮肤黑色素瘤的恶性进展过程中起重要作用,其表达程度可作为判断黑色素瘤恶性程度及预后的指标之一。     

S-100 protein-positive Langerhans cells in various human lung cancers,especially in peripheral adenocarcinomas

Summary The appearance of S-100 protein-positive Langerhans cells was studied in 90 cases of various lung cancers by an immunohistochemical method. S-100 protein-positive dendritic cells were frequently observed in many adenocarcinomas, especially in those subclassified as bronchiolar cell or type II alveolar cell type. However, no S-100 protein-positive cells were found in goblet cell type adenocarcinoma. In some cases of squamous cell carcinoma and large cell carcinoma, these dendritic cells were also observed though they were fewer in number. In all cases of small cell carcinoma, however, S-100 protein-positive dendritic cells were rare. Electron microscopic study of two adenocarcinomas clearly demonstrated many Birbeck granules in the cytoplasm of S-100 protein-positive dendritic cells and confirmed that S-100 protein-positive cells in lung cancer were identical with Langerhans cells.     

Neurospecific S-100 protein in synaptosomes of the rat cerebral cortex

A nonspecific S-100 protein was found in the composition of low-molecular-weight acid proteins from synaptosomes of the rat cerebral cortex by capillary microdisc electrophoresis in 15% polyacrylamide gel with 0.1% sodium dodecysulfate and with the aid of a highly purified marker protein. The S-100 protein accounted for 15–20% of the lowmolecular-weight acid synaptosomal proteins.Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. S. Il'in). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 164–166, February, 1976.     

S-100 antigen labels neoplastic cells in liposarcoma and cartilaginous tumours

Summary S-100 antigen, originally believed to be unique to the nervous system, has recently been found in cell types of non-neuroectodermal origin such as chondrocytes and adipocytes. These findings suggested the possibility of detecting the antigen in tumours derived from such cells. Using the PAP method and an anti-ox brain S-100, the antigen was found in the cells of human chondrosarcomas, chondroblastomas and liposarcomas. In contrast, fibrous histiocytomas and fibrosarcomas, tested to verify the cellular specificity of the S-100 immunoreaction, did not exhibit S-100-containing cell types. The present data indicate the usefulness of the S-100 antigen as a diagnostic and investigative tool in defined neoplasms of non-neuroectodermal origin, such as chondroid tumours and liposarcoma.