Neuroendocrine differentiation in adrenocortical carcinoma. New immunohistochemical findings supported by electron microscopy.

Ten adrenocortical carcinomas including two tumors with clinically detectable corticosteroid production, were immunohistochemically analyzed for their intermediate filament proteins, and for neuroendocrine markers. Keratins were present in 6 of 10, vimentin in all 10, and the 68 kilodalton kD neurofilament subunit protein in 6/10 tumors. Keratins numbers 8 and 18 were most prevalent, whereas only traces of keratins 19 and 7 were found. Eight tumors were positive for synaptophysin at least focally, and 3 showed extensive positivity in more than 30% of tumor cells. The tumors showed approximately similar levels of neuron-specific enolase (NSE) expression as judged by immunohistochemistry. Chromogranin was not detected, and there was no immunoreactivity for 3 neuropeptides (calcitonin, gastrin, somatostatin). In normal adrenal cortex, neuron-specific enolase, synaptophysin and neurofilaments were restricted to the nerves seen between the cortical cells. Electron microscopy revealed clusters of dense-core granules in 4 of 5 tumors, consistent with neuroendocrine granules. These results indicate that adrenocortical carcinomas may show signs of neuroendocrine differentiation and share some features with the adrenal medullary tumors.     

Intermediate filament proteins in human testis and testicular germ-cell tumors

Normal testicular tissue and 76 testicular germ-cell tumors of various types were immunohistochemically evaluated for the expression of intermediate filament proteins of different types. In normal testes, the rete testis epithelium was positive to cytokeratin, and the Sertoli cells, stromal cells, and Leydig cells were positive for vimentin. Cytokeratin-positive cells were also found lining atrophic seminiferous tubules and were occasionally seen within nonatrophic seminiferous tubules. The classical seminomas showed vimentin positivity, but this was usually observed in a small number of tumor cells. In addition, nearly half the seminomas contained single cytokeratin-positive cells, some of which were multinucleated and appeared to represent syncytiotrophoblastic giant cells. The tumor cells in embryonal carcinomas, endodermal sinus tumors, and choriocarcinomas displayed cytokeratin positivity. In some embryonal carcinomas vimentin-positive tumor cells were also found, probably representing attempts at further differentiation of the tumor cells. In immature teratomas, both the immature and the mature epithelial structures showed cytokeratin positivity. The stromal components, including cartilage, contained vimentin, and the smooth-muscle elements, desmin. Neural tissue positive for neurofilaments and glial tissue positive for glial fibrillary acidic protein, were observed in 5 and 3 of 15 cases, respectively. It is considered that antibodies to intermediate filaments are suitable tools to characterize the differentiation patterns of testicular germ-cell tumors and have the potential to aid in the differential diagnosis especially between seminoma and embryonal carcinoma.     

Expression of intermediate filament proteins in thyroid gland and thyroid tumors

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.     

A103 immunostaining in the diagnosis of adrenal cortical tumors: an immunohistochemical study of 316 cases

CONTEXT: The monoclonal antibody A103 recognizes an antigen on melanoma cells known as Melan-A or MART-1. Recent studies have shown that A103 also reacts with adrenal cortical cells and may be useful in the diagnosis of adrenal cortical tumors. However, only small numbers of some of the tumors in the differential diagnosis of adrenal cortical neoplasms have been studied. OBJECTIVE: To study the specificity of A103 immunohistochemistry in a large number of tumors in the differential diagnosis of adrenal cortical neoplasms. DESIGN: Formalin-fixed, paraffin-embedded tissue from 21 adrenal cortical tumors, 16 cases of metastatic carcinoma to the adrenal, 10 pheochromocytomas, and 269 extra-adrenal carcinomas was evaluated for A103 immunoreactivity using a commercially available antibody (Novocastra, Newcastle, UK). RESULTS: Positive staining was seen in all of the adrenal cortical tumors but in none of the adrenal metastases or pheochromocytomas. In the 269 extra-adrenal carcinomas, A103 immunoreactivity was limited to a single ovarian serous carcinoma. CONCLUSION: A103 immunostaining is useful in distinguishing adrenal cortical neoplasms from other carcinomas and pheochromocytoma.     

Expression of intermediate filaments in neuroendocrine tumors

Expression of 160-kilodalton (kd) neurofilament, cytokeratin, and vimentin was immunohistochemically investigated in 45 pheochromocytomas, 12 medullary thyroid carcinomas, and 12 pancreatic islet cell tumors. Four mixed neuroendocrine-neural tumors, two multiple endocrine neoplasia type I tumors, and two multiple endocrine neoplasia type II tumors were included in this study. Neurofilament immunoreactivity was demonstrated in 45 (100%) of the pheochromocytomas, 10 (83%) of the medullary thyroid carcinomas, and 11 (92%) of the islet cell tumors. Cytokeratin and vimentin were detectable in 29% and 24% of the pheochromocytomas, 100% and 25% of the medullary thyroid carcinomas, and 67% and 25% of the islet cell tumors, respectively. Neurofilament was the most frequently detected intermediate filament in the neuroendocrine tumors. Cytokeratin was seen in the intra-adrenal but not the extra-adrenal pheochromocytomas. Coexpression of neurofilament and cytokeratin was common in the neuroendocrine tumors, and occasionally vimentin was also expressed simultaneously. There were no characteristic differences in the expression of intermediate filaments between multiple endocrine neoplasia type I or II tumors and sporadic-type tumors or between metastatic tumors and nonmetastatic tumors.     

Galanin immunoreactivity in neuroendocrine tumors.

We investigated immunoreactivity for galanin, a 29-amino acid peptide, in formalin-fixed, paraffin-embedded sections of 123 neuroendocrine tumors. Galanin-immunoreactive cells were found in one of 12 hypothalamic gangliocytomas, nine of 18 adrenal pheochromocytomas, nine of 14 pituitary corticotroph adenomas, and one of two thymic endocrine tumors. In pheochromocytomas, galanin-immunoreactive cells were seen either singly or in clusters. In corticotroph adenomas, many tumor cells were positive for galanin, indicating colocalization of corticotropin and galanin in the same tumor cells. No galanin-immunoreactive cells were noted in four extra-adrenal paragangliomas; 10 medullary carcinomas of the thyroid; 35 endocrine tumors arising in the lung, pancreas, and gastrointestinal tract; and 28 pituitary adenomas composed of cells other than corticotrophs. In nontumorous counterparts of these neuroendocrine tumors, galanin immunoreactivity was observed in nerve cells of the hypothalamus, nerve fibers of the duodenum, and adenohypophyseal cells corresponding to corticotrophs. These findings indicate that galanin expression in neuroendocrine tumors is uncommon and restricted to some tumor types.     

Coexpression of intermediate filaments in squamous cell carcinomas of upper aerodigestive tract before and after radiation and chemotherapy

Frozen sections of 48 squamous cell carcinomas and seven undifferentiated carcinomas of the upper aerodigestive tract were investigated immunohistochemically with monoclonal antibodies specific for keratin, vimentin, desmin, neurofilaments, and glial fibrillary acidic proteins. In nine squamous cell carcinomas (19%) and six undifferentiated carcinomas (86%) obtained before treatment coexpression of keratin and vimentin was detected in some tumor cells by double immunofluorescence studies. Nine squamous cell carcinomas expressed neurofilaments in scattered tumor cells. Coexpression of vimentin or neurofilaments was seen especially in the peripheral cell layer of the tumor nests and did not seem to correlate with the degree of differentiation. Three undifferentiated carcinomas additionally expressed desmin, and one tumor contained neurofilaments. Glial fibrillary acidic proteins were not detected. Increased coexpression of keratin with vimentin, desmin, or neurofilaments was seen in some tumors that were studied before and after radiation/chemotherapy, suggesting that the intermediate filament profile of tumor cells can be altered by external influences.     

Expression of cytokeratins in gliomas

Metastatic carcinoma, which is a common malignant tumor seen in the central nervous system is often difficult to distinguish from glioblastoma multiforme. In general, neoplastic cells maintain fidelity in the expression of parent cell intermediate filament and immunohistochemistry remains the mainstay in diagnosis. A panel consisting of GFAP (usually positive for astrocytic tumors) and cytokeratin (usually positive for metastatic carcinomas) is most commonly used for this purpose. However, co-expression of two or more classes of intermediate filament proteins by neoplasms is a widespread phenomenon and there are reports of glial neoplasms expressing keratin markers. Our aims and objectives were to analyse the expression of both cytokeratin and GFAP in different glial tumors and metastatic carcinomas. Cases were collected for a period of two years. All the cases were diagnosed as primary or metastatic intracranial tumors. Formalin-fixed paraffin-embedded thin sections were taken on egg-albumin coated slides and immunostaining with GFAP and polyclonal cytokeratin was done. Forty-five tumors were analysed, including 35 glial neoplasms and 10 metastatic carcinomas of which 7 of the 32 astrocytic neoplasms (22%) showed focal immunoreactivity with pancytokeratin. All of the glial tumors but none of the metastatic carcinomas were positive with GFAP. So our conclusion was that co-expression of GFAP and CK is a fairly common phenomenon, especially in case of undifferentiated and high grade gliomas and this must be kept in mind while differentiating these cases from metastatic carcinoma, as CK positivity does not rule out the diagnosis of a glial neoplasm. Further studies with an expanded panel of CK is most useful for this.     

The role of calretinin, inhibin, melan-A, BCL-2, and C-kit in differentiating adrenal cortical and medullary tumors: an immunohistochemical study.

Morphologic distinction between adrenal cortical and medullary tumors can be difficult. Previous studies have shown inhibin, melan-A, and BCL-2 to be useful markers for adrenal cortical tumors. We have recently observed a high level of calretinin expression in normal adrenal cortex but not the medulla and therefore evaluated its diagnostic application for adrenal tumors in comparison with inhibin, melan-A, and BCL-2. C-kit is a transmembrane tyrosine kinase receptor. Immunodetection of c-kit expression has been recently used for tumor diagnosis, and c-kit-positive tumors can potentially benefit from kit kinase inhibitor treatment. Although c-kit expression was reported in adrenal medulla and pheochromocytoma, it has not been evaluated in adrenal cortical tumors. In this study, 28 adrenal cortical tumors (12 carcinomas, 16 adenomas), 20 pheochromocytomas, and 20 extraadrenal paragangliomas were evaluated for calretinin, inhibin, melan-A, BCL-2, and c-kit expression by standard immunohistochemical assays on paraffin sections. The percentage of immunoreactivity in adrenal cortical tumors was as follows: calretinin, 96%; melan-A, 89%; inhibin, 92%; BCL-2, 20%; and c-kit, 5%. Normal adrenal medulla did not stain for c-kit but was positive for BCL-2. Eighty-six percent of pheochromocytomas stained for BCL-2 and none for calretinin, with the exception of the ganglioneuromatous areas in composite pheochromocytomas (n = 5). Extraadrenal paragangliomas showed reactivity with calretinin in 25%, melan-A in 5%, inhibin in 16%, BCL-2 in 38%, and c-kit in 8% of the cases. Our results indicate that calretinin is the most sensitive among all the adrenal markers tested. Like melan-A and inhibin, calretinin is also a very specific marker in differentiating cortical from medullary adrenal tumors. In addition, calretinin can be used to confirm a composite pheochromocytoma. BCL-2 does not appear to be useful in differentiating adrenal cortical from medullary tumors. C-kit is not useful in the diagnosis of adrenal tumors, and kit kinase inhibitor might have a limited role in the treatment of adrenal tumors and paraganglioma because of the low frequency of c-kit expression in these tumors.     

Varying expression of cytokeratin and neurofilaments in neuroendocrine tumors of human gastrointestinal tract

Twelve cases of gastrointestinal neuroendocrine tumors, including eight carcinoids and four pancreatic islet cell tumors or their metastases, were immunohistochemically analyzed for the expression of different types of intermediate filament proteins. All of the tumors showed cytokeratin positivity in immunostaining, and the Western blotting technique revealed 45- and 52-kilodalton cytokeratins in carcinoid tumors. Three of the islet cell tumors, but none of the carcinoid tumors, showed, in addition, varying numbers of neurofilament-positive tumor cells when evaluated with rabbit and mouse monoclonal antineurofilament antibodies. The presence of only the 70-kilodalton neurofilament and cytokeratin polypeptides in an islet cell tumor was revealed also by using the Western blotting technique. On the other hand, both fetal and adult pancreatic islet cells showed only cytokeratin positivity. Neurofilament-positive epithelial cells were not found in normal small intestines either. The results show epithelial characteristics in normal gastrointestinal neuroendocrine cells and neuroendocrine tumors by their expression of cytokeratin. In addition, some islet cell tumors display the 70-kilodalton neurofilament protein which suggests the acquisition of a new type of intermediate filament during the neoplastic change.     

Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas.

The expression patterns of intermediate filament proteins of primary and metastatic endometrial (n = 18) and ovarian (n = 24) adenocarcinomas were analyzed by immunocytochemistry using a panel of specific antibodies and by gel electrophoresis of cytoskeletal preparations, followed by immunoblotting. All cells of all endometrial adenocarcinomas studied contained the "simple epithelial"-type cytokeratins (CKs) 8, 18, and (mostly) 19, with variable numbers of cells also positive for CK 7 and vimentin. In addition, most of these tumors contained individual cells or groups of cells that were positive for the stratification-related CKs 4, 5, 6, 13, 14, and 17. The latter CKs were often associated with squamous cell foci, but were also found in some single (nonsquamous) tumor cells, indicative of early stages of squamous cell differentiation. Ovarian carcinomas of various histologic types and grades contained predominantly CKs 7, 8, 18, and 19. Serous, endometrioid, and anaplastic tumors, but not mucinous and clear cell tumors, also contained minor amounts of stratification-related CKs in variable combinations, mostly including CK 4. In all tumor types except mucinous tumors, vimentin was consistently detected in variable proportions of tumor cells which, however, were rather low in anaplastic carcinomas. Surprisingly, glial filament protein was detected in a minor proportion (< or = 20%) of tumor cells in seven of 14 serous and endometrioid ovarian carcinomas and in three of 18 endometrial carcinomas. These different intermediate filament expression patterns of müllerian duct-type carcinomas, only partly related to the morphologic appearance of the specific type of tumor, might reflect the multipotentiality of differentiation of müllerian duct-derived epithelia. Cytoskeletal features of potential diagnostic value, especially in metastatic carcinomas, are discussed.     

Diagnostic value of intermediate filament antibodies in clinical cytology

Summary Antibodies to intermediate filament (IF) proteins can distinguish the major tumor groups as shown by results with sectioned human material. In this study we evaluate the use of similar methods in the cytology of human tumors. Smears obtained from fine needle aspiration biopsies were investigated using well characterized antibodies, each specific for only one of the five types of intermediate filaments. Tumor cells of different carcinomas, thymomas, and the epithelial part of pulmonary blastomas were positive with antibodies recognizing cytokeratins. Tumor cells in non-muscle sarcomas, including lymphoma and Ewing's sarcoma, could be specifically identified with antibodies to vimentin. Tumor cells of muscle sarcomas were desmin-positive. Finally, tumor cells in pheochromocytoma and bronchus carcinoid were positive with antibodies specific for neurofilaments. Specimens were also examined in parallel using conventional cytochemical stains, such as May-Grünwald-Giemsa. In addition, in most cases sections of the tumor were examined both by histology and IF typing of frozen sections to confirm the diagnosis made on the cytologic specimens. The results show that IF typing is a valuable diagnostic aid in clinical cytology.     

Cell differentiation in sacrococcygeal teratomas. An immunohistochemical and follow-up study.

The cell differentiation properties of thirty-four sacrococcygeal teratomas (SCT) and their five recurrences were immunohistochemically studied for the expression of different classes of intermediate filament proteins, muscle actin (MA) and S-100 protein. Out of thirty-nine tumors twenty-three were SCTs with only mature tissue elements, seven immature teratomas, five pure endodermal sinus tumors (EST) and four ESTs or embryonal carcinomas (EC) combined with mature components. Cytokeratin positivity was found in all epithelial structures and sometimes also in smooth muscle and primitive mesenchymal cells. An intense cytokeratin immunoreactivity was observed in EC and EST components. Muscle markers, desmin and MA were present in smooth and striated muscle cells. Focal desmin positivity was also found in some epithelial structures in two cases. Glial tissue positive for glial fibrillary acidic protein (GFAP) was found in twenty-eight out of thirty-nine tumors. Some cases with no apparent glial tissue in hematoxylin and eosin staining showed glial differentiation as proved by GFAP positivity. In six out of eleven choroid plexus-like tissues GFAP positive cells were observed. S-100 protein showed an intense distribution of immunoreactivity outside neural tissue, and focal positivity was observed in malignant epithelial structures. Immunohistochemical markers did not reveal any prognostic significance in teratomas. Our findings, however, showed some aberrant features of cell differentiation from normal mature tissue components but closely parallel to those found in normal fetal development.     

Malignant fibrous histiocytoma. Heterogeneous patterns of intermediate filament proteins by immunohistochemistry

Patterns of intermediate filament expression of 10 malignant fibrous histiocytomas (MFHs) were immunohistochemically evaluated using acetone-fixed frozen sections. Seven cases represented the storiform-pleomorphic subtype, 2 were of myxoid type, and 1 was of giant-cell type. All cases had been studied by electron microscopy, and no proof for the diagnoses of liposarcoma, rhabdomyosarcoma, and leiomyosarcoma could be obtained. All tumors showed prominent vimentin immunoreactivity in the tumor cells. Cytokeratin-positive neoplastic cells were found in 2 cases, and in the majority of tumor cells in 1 of these. The 68k neurofilament-positive cells were found in 2 cases. Desmin was not found beyond doubt in the neoplastic cells in any cases, and all cases were negative for glial fibrillary acidic protein. The expression of several types of intermediate filament indicates divergent differentiation properties in MFH and may suggest the heterogeneity of this entity, but more cases should be studied to elaborate any possible consistent patterns of intermediate filament expression in different types of MFH. The expression of multiple types of intermediate filament proteins in MFH can alternatively signify random activation of the corresponding genes in the primitive tumor cells. The complex patterns of intermediate filament proteins in morphologically defined MFHs should be taken into account in the practical immunohistologic analysis of tumors.     

DLK is a novel immunohistochemical marker for adrenal gland tumors

Delta-like protein (DLK) is expressed in fetal and adult adrenal glands. We have investigated if this expression is maintained in adrenal gland-derived tumors. All the studied 37 cortical tumors, including five carcinomas, stained positively as well as the 13 examined pheochromocytomas. Thus, DLK is a very sensitive marker for adrenal tumors of cortical and medullary origin. Renal cell carcinomas, presenting the major differential diagnostic problem for cortical tumors, were all negative, as well as melanomas, which are similar to high portion of adrenocortical tumors that react with melan-A. However, all paragangliomas, some carcinoids, and thyroid medullary carcinomas were also positive for DLK. Therefore, this novel immunohistochemical marker seems useful for the identification of adrenocortical tumors while it has limited value for the distinction of pheochromocytomas from diagnostically related neuroendocrine tumors.     

Expression of intermediate filaments in malignant fibrous histiocytomas

The expression of intermediate filaments (IFs) in 34 malignant fibrous histiocytomas (MFHs) was studied immunohistochemically and ultrastructurally. Using the avidin-biotin-peroxidase method, positive reactions were detected as follows: for desmin in 12 tumors, for neurofilament in two tumors, for cytokeratin in one tumor, and for vimentin in 30 tumors. Desmin immunoreactivity was found in tumors of all four histologic subtypes and cytokeratin immunoreactivity was found in one tumor of the myxoid type. Because of the cross-reactivity of anti-neurofilament antibody with reactive histiocytes, the immunoreactivity for neurofilament seemed to be non-specific. Ultrastructurally, five of 13 tumors studied contained some tumor cells showing myofibroblastic or smooth muscle cell differentiation. A few tumor cells in one cytokeratin-positive tumor had tonofilaments in their cytoplasm. Desmin expression in some MFHs seemed to be due to myofibroblastic or smooth muscle cell differentiation of some tumor cells. Cytokeratin expression seemed to indicate epithelial differentiation in some MFHs. This varied expression of IFs in MFHs may reflect the heterogeneous nature of MFHs, and suggests that MFHs represent the final stages of dedifferentiation of several different types of sarcomas or, alternatively, represent forms of poorly differentiated sarcoma with the potential of developing into more differentiated sarcomas of heterogeneous origin.     

An immunohistochemical study of pheochromocytomas

Twenty -six adrenal pheochromocytomas and four normal adrenal medullae were studied immunohistochemically. These included four malignant tumors with proven metastases, six tumors in patients with neurofibromatosis, nine tumors in patients with multiple endocrine neoplasia type 2, and seven sporadic nonfamilial pheochromocytomas. Immunohistochemical localization of neuron-specific enolase (NSE) was seen in all tumors and in the four normal adrenals. Methionine enkephalin-like immunoreactivity was present in tumors from all four groups and in the normal adrenals. Corticotropinlike immunoreactivity was found focally in two normal adrenal medullae and in four benign pheochromocytomas. Our results indicated that NSE was present in all four major groups of pheochromocytomas, including benign and malignant tumors. This marker aided in distinguishing between adrenal cortical and medullary tumors in unusually difficult cases, since all normal adrenal cortex and adrenal cortical tumors had negative test results for NSE.     

Ultrastructural appearance and cytoskeletal architecture of the clear, chromophilic, and chromophobe types of human renal cell carcinoma in vitro.

The clear, chromophilic, and chromophobe types of human renal cell carcinoma have been defined as distinct morphological entities and can be clearly separated by differences of ultrastructural appearance, cytoskeletal architecture, enzyme synthesis, and cytogenetic aberrations. In this report, the cytomorphological aspects of these tumor types are compared in vitro, showing that essential ultrastructural and cytoskeletal characteristics of each tumor type are expressed even after prolonged in vitro cultivation. The pattern of intermediate filament proteins of each tumor type was preserved in vitro, permitting the separation of exclusively cytokeratin-positive chromophobe tumor cells from clear and chromophilic tumor cells with a co-expression of vimentin and cytokeratins. In vitro, the chromophobe tumor cells continued to exhibit abundant cytoplasmatic microvesicles and sparsely distributed "studded" vesicles, which are known to be characteristic features of this tumor type in vivo. This observation confirmed the structural similarity of the chromophobe cell to the 'intercalated cell' of the cortical collecting duct and provided further evidence for the histogenetic derivation of this tumor subtype from the collecting duct system.     

Nerve growth factor receptor expression in peripheral and central neuroectodermal tumors, other pediatric brain tumors, and during development of the adrenal gland.

Nerve growth factor (NGF) is important to the survival, development, and differentiation of neurons. Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR). In this study, NGFR expression by human fetal and adult adrenal medullary tissue, peripheral nervous system (PNS) neuroectodermal tumors (neuroblastoma, ganglioneuroblastoma, ganglioneuroma), pediatric primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), and CNS gliomas was examined by an immunohistochemical technique. Sixty-nine tumors in total were probed in this manner. Nerve growth factor receptor immunoreactivity was confined to nerve fibers and clusters of primitive-appearing cells in the fetal adrenal, and to nerve fibers and ganglion cells of the adult adrenal medulla; adrenal chromaffin cells were negative. In PNS neuroectodermal tumors, there was NGFR expression in tumor cells of 6 of 11 neuroblastomas and 6 of 6 ganglioneuroblastomas or ganglioneuromas. Thirteen of thirty-five CNS PNETs showed NGFR positivity. In most CNS PNETs, NGFR was restricted to scattered single or small groups of cells, but two tumors with astroglial differentiation showed much more extensive immunoreactivity. Most astrocytomas (11 of 14) and all ependymomas (3 of 3) were intensely NGFR positive.     

Intermediate-filament expression in thyroid gland carcinomas

Summary Paraffin-embedded specimens of 200 primary thyroid carcinomas were examined immunohistologically for the expression of intermediate-filament (IF) protein of the cytokeratin, vimentin and neurofilament type. In 36 cases, snap-frozen tissue was available, and double label immunofluorescence microscopy was performed in 23 of them.Cytokeratin reactivity was found in all cells of all follicular, papillary and medullary carcinoma cases examined. Using a monoclonal vimentin antibody, positive staining was found in many, though not all cells of the papillary tumours and in approximately 50% of the follicular and the medullary carcinomas. Among anaplastic carcinomas, some tumours were positive for cytokeratins, with or without coexpression of vimentin. Neurofilaments could only be demonstrated in approximately 13% of medullary tumours which in general also exhibited vimentin positivity.The differences of IF expression in follicle and C-cell thyroid carcinomas and the broad variation of cytokeratin and vimentin immunoreactivity among anaplastic tumours of this organ is discussed in relation to the possible intrinsic heterogeneity of these tumours and the diagnostic value of these marker.Dedicated to Prof. Dr. G. Seifert on the occasion of his 65th birthday