Immunohistochemical study of granular cell tumors of the neurohypophysis

Six granular cell tumors (GCT) of the neurohypophysis were studied by immunohistochemical techniques. They were all labeled by peanut lectin (Arachis hypogaea) and three showed reactivity for S-100 protein. Unlike extracranial GCT, neuron specific enolase (NSE), myelin basic protein (MBP) and vimentin were not detected in the tumor cells. Glial fibrillary acidic protein (GFAP), keratin and desmin were also not observed. On the other hand, some showed reactivity for alpha-1 -antitrypsin (AAT), alpha-1-antichymotrypsin (AAC) and cathepsin B. These results suggest that neurohypophysial GCT have some features different from extracranial GCT and that they may not be derived from Schwann cells.     

Immunohistochemical study of granular cell tumors of the neurohypophysis.

Six granular cell tumors (GCT) of the neurohypophysis were studied by immunohistochemical techniques. They were all labeled by peanut lectin (Arachis hypogaea) and three showed reactivity for S-100 protein. Unlike extracranial GCT, neuron specific enolase (NSE), myelin basic protein (MBP) and vimentin were not detected in the tumor cells. Glial fibrillary acidic protein (GFAP), keratin and desmin were also not observed. On the other hand, some showed reactivity for alpha-1-antitrypsin (AAT), alpha-1-antichymotrypsin (AAC) and cathepsin B. These results suggest that neurohypophysial GCT have some features different from extracranial GCT and that they may not be derived from Schwann cells.     

Bowes human melanoma cell line. An immunocytochemical study

Bowes human melanoma cell line was investigated immunocytochemically to localize S-100 protein, HMB-45 and intermediate filament proteins. The majority of the cells showed strong positive staining with antibodies directed against S-100 protein, HMB-45 and vimentin filaments. Antibodies directed against the other cytoskeletal proteins failed to show any reactivity. These findings suggest that this transformed cell line does not dedifferentiate in culture and continues to express the specific antigens of human melanoma cells. Thus, Bowes cell line provides a useful model for studying the cellular biology and pathology of malignant melanoma.     

Immunohistochemical study of a case of malignant müllerian mixed tumor in comparison with the activity of normal uterine tissue

A case of malignant Müllerian mixed tumor of the uterus, exhibiting a histology of heterologous osteosarcomatous differentiation, is presented. Special emphasis is placed on the characteristic immunohistochemical reactivity of the tumor tissue in comparison with that of normal uterine tissue in the proliferative phase. Keratin, cytokeratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (HCG) were found only in the carcinomatous element. However, neuron specific enolase (NSE), S-100 protein (S 100) and vimentin were identified in almost all tumor tissue elements. Desmin and actin were not stained in any elements. Myoglobin was only detected weakly in the squamous carcinomatous element. Undifferentiated cell element, composed of small, round, spindle, or polygonal cells showed positive reactions to NSE and S 100, but not to any other antibodies. As compared to the reactivities of the normal proliferative endometrium, the glandular epithelial cells were positive with NSE, S 100, vimentin and CEA, but the stromal cells were only positive with vimentin. Such a multitudinous and concomitant expression of antigenicity to the different tumor elements indicates a close relationship to its mesodermal Müllerian origin, and NSE, S 100 and vimentin might be most adequate indicators of these types of tumors.     

Immunocytochemical characteristics of perivascular and intratumoral foam cells in neoplasms of neuroectodermal origin with lysozyme, alfa1-antitrypsin, protein S-100 and GFAP

Investigations were performed to become acquainted with the immunohistochemical features of foam cells localized perivascular and intratumoral in neoplasms of neuroectodermal origin. Antibodies against lysozyme (muramidase) (LO), alfa 1-antitrypsin (AT), protein S-100 and glial fibrillary acid protein (GFAP) were used. A weak or medium intense reaction result has been obtained in the cytoplasm of the foam cells if antibodies against LO, and alfa 1-antitrypsin and almost negative result if antibodies against protein S-100 and GFAP were used. Only very few cells which differ from the foam cells morphologically were very intense stained with primary antibodies against LO and alfa 1-antitrypsin. In accordance with the present views the LO and AT positive cells were recognized as macrophages. The application of macrophage markers did not allow us to ascribe unequivocally the foam cells macrophage-like or histiocyte-like properties. May be that the foam cells in tumors of perivascular and intratumoral localization present another phenotypic defined group of histiocytes, despite their morphological similarity to those cells derived from smooth muscle cells of arterial blood vessels observed in arteriosclerosis.     

嫌色性肾细胞癌与嗜酸细胞瘤的临床病理分析与比较

目的探讨嫌色性肾细胞癌(chromophobe renal cell carcinoma,CRCC)和嗜酸细胞瘤(oncocytoma)的临床病理学特征,提高对二者的认识和诊疗水平。方法对手术切除的5例CRCC和2例Oncocytoma进行肉眼和光镜观察、免疫组织化学染色,分析其临床病理学差异。结果 CRCC以实体结构为主、胞质半透明或嗜酸性颗粒状、核皱缩且核周有空晕;Oncocytoma以巢状结构为主,胞质嗜酸颗粒状、核圆形、核仁小。免疫组化染色显示两者均呈E-cadherin、EMA、CK20、vimentin阳性;CRCC瘤细胞CD10和CK7强阳性而S-100蛋白阴性,5名患者随访8~32个月,其中1例手术12个月后由于转移死亡;Oncocytoma瘤细胞S-100蛋白强阳性、CD10和CK7阴性,2名患者随访41个月,均未出现复发和转移。结论 CRCC和oncocytoma二者形态学各有特征,免疫表型相似,二者鉴别诊断主要在于生长方式和细胞学特征。综上所述:CRCC为惰性肿瘤,Oncocytoma为良性肿瘤,预后较好,手术切除后极少发生复发和转移。     

Immunohistochemical study of sensory nerve formations in human glabrous skin.

The sensory nerve formations (or corpuscles) of normal human glabrous skin from hand and fingers, obtained by punch biopsies, were studied by the streptavidin-biotin method using monoclonal antibodies directed against neurofilament protein (NFP), S-100 protein, glial fibrillary acidic protein (GFAP), cytokeratins, and vimentin. NFP immunoreactivity (IR) was observed in the central axons of most sensory formations, while S-100 protein IR was restricted to non-neuronal cells forming the so-called inner cells core or lamellar cells. Furthermore, vimentin IR was found in the same cells of Meissner's and glomerular corpuscles. None of the sensory nerve formations were stained for GFAP or keratin. The present results suggest that the main nature of the intermediate filaments of the non-neuronal cells of sensory nerve formations from human glabrous skin is represented by vimentin and not by GFAP. Thus, our findings suggest that lamellar and inner core cells of SNF are modified and specialized Schwann cells and not epithelial or perineurial derived cells.     

Immunohistochemical localization of S-100 protein, glial fibrillary acidic protein, and neuron-specific enolase in the pars distalis of quail, rat, and human hypophyses

In the present study, we have localized immunohistochemically S-100 protein, glial fibrillary acidic (GFA) protein, and neuron-specific enolase (NSE) by the unlabelled antibody peroxidase-antiperoxidase technique. Special attention was paid to the influence of fixation and of pretreatment of sections with proteolytic enzymes. It appeared that the final immunostaining of a given antigen largely depends on the fixative and on the species used. Moreover, pepsin pretreatment proved to be necessary to unmask S-100 protein in quail and GFA protein in rat. S-100 protein (rat, human) and GFA protein (human) immunoreactivities were detected in the folliculo-stellate (FS) cells. In quail, S-100 protein was also found in cells, which were not arranged around a follicular lumen and, in rat, the endothelial cells were immunostained for GFA protein. Clusters of granular cells were weakly immunostained for NSE in all species. An exclusive relationship between FS cells and S-100 protein could not be ascertained from this study.     

Immunohistochemical expression of Galectin-3 and HBME-1 in granular cell tumors: a new finding

Granular cell tumor (GCT) is a relatively rare neoplasm, usually located in the upper aerodigestive tract, skin and soft tissue. Because of its uncertain histogenesis, GCT has been the object of many immunohistochemical and ultrastructural studies that have suggested a Schwann cell origin. Our recent observation of a case of GCT immunoreactive for Galectin-3 and HBME-1 led us to further investigate the immunohistochemical profile of these neoplasms. We evaluated the immunohistochemical expression of the traditional markers for GCT (S-100, CD68) along with new markers (Galectin-3, HBME-1, Calretinina and Inhibin-alpha) in 22 granular cell tumors. Our results showed, in all cases, a constant diffuse positivity for S-100 protein, CD68 and Galectin-3. HBME-1 was positive in 95% of cases. The present study gives a new immunophenotypic profile for GCT, which could help pathologists in distinguishing morphologically ambiguous granular lesions in unusual sites.     

Characterization of glycoconjugates found in granular cell tumors, with special reference to keratan sulfate

Nine granular cell tumors (GCTs) were studied using the immunoperoxidase technique with a mouse monoclonal antibody to keratan sulfate and a polyclonal antibody to S-100 protein. Various lectins and basic dye stains were also employed. Schwannomas benign and a malignant, a neurofibroma, a leiomyoma, two examples of nevus pigmentosus and a congenital epulis were similarly examined to compare the histochemical reactivities. Tumor cells of all the GCTs reacted intensely with the antibodies to keratan sulfate and S-100 protein. Peripheral nerve bundles and other neurogenic tumors showed stained for S-100 protein but not for keratan sulfate. Basic dye stain indicated the presence of sulfated glycoconjugates in GCTs. Lectin stains demonstrated that GCTs were rich in glycoconjugates but the reactivity patterns for 14 lectins differed between GCTs and normal tissue components. None of the lectins used in this study was specific for GCTs. These results indicate that GCTs contain abundant glycoconjugates and that the monoclonal antibody to keratan sulfate may be an immunohistochemical marker for GCT.     

S-100 protein and neuron-specific enolase in parathyroid glands and C-cells of the thyroid

Normal parathyroid glands and parafollicular cells (C-cells) of man, rat and rabbit, and also human parathyroid adenomas and medullary carcinomas were investigated for the presence of S-100 protein and neuron-specific enolase (NSE). For determination of the proteins immunoperoxidase methods were applied, i.e., the PAP method and the avidin-biotin system. The antisera, of polyclonal origin, were specifically directed against cow S-100 protein and rat or bovine NSE. The respective antisera are known to crossreact with S-100 protein from man, rat, and rabbit, as well as with NSE from man and rat. Surprisingly, the test for S-100 protein was found to be strongly positive in the parathyroid glands of rat and rabbit and was focally positive in normal and adenomatous human parathyroid glands, but completely negative in C-cells and medullary carcinoma cells. NSE was present in C-cells of rat and man, and in medullary carcinoma cells, but was absent in normal and adenomatous parathyroid cells. The results support data that indicate that both parathyroid cells and C-cells are derived from elements of the neural crest, but undergo different maturation processes during embryological development.     

S-100 protein and neuron-specific enolase in parathyroid glands and C-cells of the thyroid

Summary Normal parathyroid glands and parafollicular cells (C-cells) of man, rat and rabbit, and also human parathyroid adenomas and medullary carcinomas were investigated for the presence of S-100 protein and neuron-specific enolase (NSE). For determination of the proteins immuno-peroxidase methods were applied, i.e., the PAP method and the avidin-biotin system. The antisera, of polyclonal origin, were specifically directed against cow S-100 protein and rat or bovine NSE. The respective antisera are known to crossreact with S-100 protein from man, rat, and rabbit, as well as with NSE from man and rat. Surprisingly, the test for S-100 protein was found to be strongly positive in the parathyroid glands of rat and rabbit and was focally positive in normal and adenomatous human parathyroid glands, but completely negative in C-cells and medullary carcinoma cells. NSE was present in C-cells of rat and man, and in medullary carcinoma cells, but was absent in normal and adenomatous parathyroid cells. The results support data that indicate that both parathyroid cells and C-cells are derived from elements of the neural crest, but undergo different maturation processes during embryological development.     

Immunohistochemical localization of S-100 protein,glial fibrillary acidic protein,and neuron-specific enolase in the pars distalis of quail,rat, and human hypophyses

Summary In the present study, we have localized immunohistochemically S-100 protein, glial fibrillary acidic (GFA) protein, and neuron-specific enolase (NSE) by the unlabelled antibody peroxidase-antiperoxidase technique. Special attention was paid to the influence of fixation and of pretreatment of sections with proteolytic enzymes. It appeared that the final immunostaining of a given antigen largely depends on the fixative and on the species used. Moreover, pepsin pretreatment proved to be necessary to unmask S-100 protein in quail and GFA protein in rat. S-100 protein (rat, human) and GFA protein (human) immunoreactivities were detected in the folliculo-stellate (FS) cells. In quail, S-100 protein was also found in cells, which were not arranged around a follicular lumen and, in rat, the endothelial cells were immunostained for GFA protein. Clusters of granular cells were weakly immunostained for NSE in all species. An exclusive relationship between FS cells and S-100 protein could not be ascertained from this study.     

Inflammatory pseudotumour of the lung. Immunohistochemical analysis on four new cases

Inflammatory pseudotumour of the lung (I.P.) is a quite rare benign lesion, variously named by different authors. In the present report four new cases of I.P. are presented and immunohistochemically studied with a panel of antibodies. Microscopically, the most prominent histological features were the presence of interlacing bundles of elongated histiocytic-like cells, plasma cell aggregates and lymphoid follicles. Immunohistochemistry showed that plasma cells are polyclonal. The spindle cells were negative for desmin, cytokeratins, lysozyme and S-100 and immunoreactive for alpha-1-antichymotrypsin, vimentin and for smooth-muscle alpha-actin. Actin and desmin, were clearly evident in the vessels' smooth muscle layers, highlighting the angioinvasive behaviour of the lesions. Our data are in keeping with literature suggesting that I.P. is due to a mixed histiocytic-myofibroblastic-reactive proliferation and support the inflammatory nature of IP.     

Pleomorphic ("dedifferentiated") chondrosarcoma. Report of a case initially examined by fine needle aspiration biopsy

Fine needle aspiration (FNA) biopsy of a predominantly radiolucent, destructive lesion of the right distal femoral metaphysis of a 69-year-old man produced smears containing spindle-shaped cells with cytologic features consistent with a malignant fibrous histiocytoma. This initial diagnosis was supported by immunoperoxidase staining, which was strongly positive for vimentin and alpha-1-antichymotrypsin, focally positive for S-100 protein and negative for desmin, muscle-specific actin, keratin, carcinoembryonic antigen and epithelial membrane antigen. Subsequent surgical resection revealed a lesion with a predominance of malignant fibrous histiocytoma-type regions; however, focal microscopic areas contained a low-to-medium-grade cartilaginous component. The final diagnosis rendered was thus pleomorphic or so-called "dedifferentiated" chondrosarcoma. This rare lesion should be included in the differential diagnosis of malignant spindle-cell lesions of bone assessed by FNA biopsy.     

Identification and characterization of a human cell line with dendritic cell features

CORP-4 is a cell line obtained in our laboratory from an explanted human bladder carcinoma. This cell line shows certain dendritic cell features such as adherence to the culture plate surface, a doubling time of 24 h and an enzymatic profile typical of cells involved in antigen presentation (non-specific esterases, lysozyme and alpha-1-antitrypsin). Its phenotypic analysis revealed CD 15 and Fc receptor expression, S-100 surface protein and the presence of positive reactivity to different lectins such as Concanavalin A (Con A) and Peanut agglutinin (PNA). CORP-4 was found to be a non-phagocytic cell line after it was assayed with latex, and FcR- and C3bR-mediated phagocytosis. Furthermore, CORP-4 produced interleukin-1 (IL-1) as determined by thymocyte proliferation assays and also fixes immune complexes in a non-complement dependent fashion. HLA class I and class II antigens were inducible by both 5 azacytidine and gamma interferon.     

Multiple expression of keratins, vimentin, and S-100 protein in pleomorphic salivary adenomas.

Immunohistochemical staining for S-100 protein and the intermediate filaments keratin and vimentin, was made in 41 salivary adenomas. In pleomorphic adenomas, great heterogeneity in the staining, as well as multiple and co-expressions of these proteins were found in the outer tumor cells of tubulo-ductal structures and modified myoepithelial cells, but not in the luminal tumor cells. All the outer tumor cells stained for S-100 protein, 97% for K8.12 keratin and 85% for vimentin. Of these cells, 29% showed multiple expression of K8.12 keratin, vimentin, and S-100 protein, and 17% showed co-expression of K8.12 and S-100 protein. Modified and neoplastic myoepithelial cells showed similar expressions of these proteins to those of outer tumor cells; myoepithelioma cells displayed the most complicated pattern, being positive for KL1, PKK1, and K8.12 keratins, vimentin and S-100 protein. In luminal tumor cells there was a heterogeneous expression of KL1 and PKK1 in 82%, and of KL1, PKK1, and K8.12 in only 14.7%. Based on the immunohistochemical findings obtained with different monoclonal antibodies in pleomorphic salivary adenomas, outer tumor cells may be derived from ductal basal cells and luminal tumor cells from intercalated duct cells.     

Multiple expression of keratins,vimentin, and S-100 protein in pleomorphic salivary adenomas

Immunohistochemical staining for S-100 protein and the intermediate filaments keratin and vimentin, was made in 41 salivary adenomas. In pleomorphic adenomas, great heterogeneity in the staining, as well as multiple and co-expressions of these proteins were found in the outer tumor cells of tubulo-ductal structures and modified myoepithelial cells, but not in the luminal tumor cells. All the outer tumor cells stained for S-100 protein, 97% for K8.12 keratin and 85% for vimentin. Of these cells, 29% showed multiple expression of K8.12 keratin, vimentin, and S-100 protein, and 17% showed co-expression of K8.12 and S-100 protein. Modified and neoplastic myoepithelial cells showed similar expressions of these proteins to those of outer tumor cells; myoepithelioma cells displayed the most complicated pattern, being positive for KL1, PKK1, and K8.12 keratins, vimentin and S-100 protein. In luminal tumor cells there was a heterogeneous expression of KL1 and PKK1 in 82%, and of KL1, PKK1, and K8.12 in only 14.7%. Based on the immunohistochemical findings obtained with different monoclonal antibodies in pleomorphic salivary adenomas, outer tumor cells may be derived from ductal basal cells and luminal tumor cells from intercalated duct cells.     

Changes in the levels of neural cell specific proteins in the developing rat brain

The levels of S-100 protein (S-100) and neuron-specific enolase (NSE) in the developing rat brain were determined by a sensitive enzyme immunoassay and the results were compared with those obtained by other methods. Changes with development in the levels of S-100, NSE, and 2, 3-cyclic nucleotide 3-phosphodiesterase (CNPase), biochemical markers for astroglia, neurons and oligodendroglia respectively, were determined in various brain regions including the cerebral hemisphere (CH), brain stem (BS) and cerebellum (Ce). The peak increments of S-100, NSE, and CNPase activity were reached later than that of the brain weight in all of the regions. The ratios of S-100/NSE and CNPase/NSE rose during the 21 days after birth in the CH and BS; the S-100/NSE ratio in the CH began to decrease from the 21st day, whereas the CNPase/NSE ratio continued to rise even after the 30th day, suggesting different maturation periods of the different glial cells. In the Ce, the change of these ratios showed a pattern different from those in the other regions. In the CH of rats with experimental microencephaly induced by methylazoxymethanol (MAM), the ratios were almost normal, in spite of the reduction of the brain weight to about 50% of the control.Dedicated to Professor Yasuzo Tsukada.     

Serum concentration of alpha-2-macroglobulin, alpha-1-antitrypsin and alpha-2-antichymotrypsin in patients with lung carcinoma

Serum concentration of alpha-2-macroglobulin, alpha-1-antitrypsin and alpha-2-antichymotrypsin was evaluated in 26 patients with lung carcinoma. We observed an evident decrease in alpha-2-M and alpha-1-antitrypsin level and no differences between tested and control groups in alpha-1-antichymotrypsin concentration. The deficiency of protease inhibitors may be due to the increased level of protease activity in malignant cells. Infiltration of granulocytes near tumor and released enzymes from them may exhaust proteolytic inhibitory capacity, too. Increased protease activity is associated with transformation and uncontrolled proliferation, therefore antiproteases may be accepted as anticancerogenic factors. Further investigations are needed to bring us closer to understanding this question.