Intermediate filaments and their interaction with membranes. The desmosome-cytokeratin filament complex and epithelial differentiation

Intermediate-sized filaments represent a class of morphologically similar but biochemically and immunologically distinguishable cytoplasmic protein polymer structures. Five major filament types have been identified (cytokeratin, vimentin, desmin, neurofilament protein, glia filament protein) and antibodies to these proteins have been used for distinguishing different cell types and tumors derived therefrom. Epithelial and carcinoma cells are characterized by the presence of cytokeratin filaments and desmosomal elements identified by antibodies to certain high molecular weight proteins of desmosomal plaques. However, the specific pattern of cytokeratin polypeptides is different in different epithelia. The potential value of cell type identification by immunological reactions with antibodies to cytoskeletal proteins in tumor diagnosis is discussed.     

Antidesmosomal monoclonal antibody in the diagnosis of intracranial tumours

Immunocytochemistry has been applied extensively to the diagnosis of intracranial tumours, but meningiomas still present a diagnostic problem. However, desmosomes have been shown by electron microscopy to be present in meningiomas, and this distinguishes them from gliomas. This paper describes a new monoclonal antibody, 11-5F, against desmosomal proteins 1 and 2 (desmoplakins) and assesses its usefulness in the diagnosis of meningiomas and other intracranial tumours. A total of 74 surgically removed intracranial tumours were examined by fluorescent antibody staining with 11-5F on frozen sections. In addition, a panel of antibodies against cytokeratin, vimentin, glial fibrillary acidic protein, and S100 protein was used. 11-5F stained 30/30 meningiomas and 14/14 metastatic carcinomas but 0/30 gliomas, thus distinguishing meningiomas and metastatic carcinomas from gliomas. The distinction between meningiomas and metastatic carcinomas on the basis of intermediate filaments staining was more difficult because neither the anticytokeratin nor the antivimentin antibody was specific for either tumour type. This study emphasizes the value of antidesmosomal antibodies as an important adjunct to the diagnosis of intracranial tumours.     

Intracranial tumours in budgerigars

In a retrospective study of 996 budgerigars 14 intracranial tumours were examined histologically and immunocytochemically. Tumours of the ependyma (6), choroid plexus (1), adenohypophysis (6) and one unclassified tumour were found. Immunostaining was applied using antibodies against glial fibrillary acidic protein, vimentin, cytokeratin, neuron specific enolase, neurofilament-200 and S-100 protein. The presence of hormones in pituitary tumours was also tested by immunocytochemistry with antibodies to adrenocorticotrophic hormone, melanocyte-stimulating hormone, prolactin and growth hormone. Positive immunostaining was found in two carcinomas of the adenohypophysis using anti-growth hormone antibody and, by using anti-S-100 antibody, in the cytoplasm of several cells of the remaining tumours. There was no immunoreactivity in either normal or neoplastic tissues of budgerigars with anti-glial fibrillary acidic protein, anti-vimentin, anti-cytokeratin and anti-neuron specific enolase antibodies. With anti-neurofilament-200 antibody, positive immunoreactivity was found in neuronal fibres of normal brain but not in neoplastic tissue.     

Intermediate filaments and desmosomal plaque proteins in testicular seminomas and non-seminomatous germ cell tumours as revealed by immunohistochemistry

Summary Seminomas and non-seminomatous testicular germ cell tumours were studied for the presence of cytokeratin and vimentin filaments and desmosomes using immunohistochemical methods. In the majority of the classical seminomas and in seminomatous areas of mixed tumours most tumour cells appeared to lack cytokeratin filaments. Some seminomas contained a focally variable proportion of cells exhibiting cytokeratin-positive structures while other cases contained only few seminoma cells with a well developed fibrillar cytokeratin network. Gel electrophoresis of cytoskeletal proteins from microdissected regions revealed cytokeratin polypeptides nos. 8 and 18 typical of simple epithelia. In one seminoma, however, all, or almost all, tumour cells contained cytokeratin filaments. This finding is in line with the assumption of transitional forms between seminoma and embryonal carcinoma. Despite the lack - or variable expression - of cytokeratin filaments most seminoma cells contained desmosomes, although often few in number and irregularly distributed at the circumference of the cells. Loosely arranged and often very sparse vimentin fibrils were found in many, but not all seminoma cells. Double label immunofluorescence microscopy suggested that the majority of desmosomes was associated with intermediate filaments of the vimentin type. In contrast, in carcinoma cells of malignant teratomas, in well differentiated epithelial cells of intermediate-type malignant teratomas and in trophoblastic cells present in trophoblastic-type malignant teratomas cytokeratin filament bundles as well as desmosomes were decorated. The arrangement and density of the cytokeratin filament skeleton and of desmosomes varied with degree of maturation of the tissue. The most regular distribution and intensive staining of cytokeratin filaments and desmoplakin was found in mature tissues. Vimentin was demonstrated in mesenchymal areas and stroma cells. The results show that seminomas are distinguished from most other germ cell and non-germ cell tumours by the presence of true desmosomes together with scanty vimentin filaments in most tumour cells. In addition, they indicate that seminoma cells can be heterogenous in their cytoskeletal complement and may include cells with cytokeratin expression, indicative of a multi-potential character of the initially transformed cell(s).Supported in part by Fonds Zur Förderung der wissenschaftlichen Forschung (grant No. 4708 to H.D) and by the Deutsche Forschungsgemeinschaft (grants Mo 345/3 and Fr 308-17)     

Immunocytochemical demonstration of intermediate filament cytoskeleton proteins in human endocrine tissues and (neuro-) endocrine tumours

Summary The presence and distribution of intermediate filament proteins, such as cytokeratins, vimentin, neurofilament proteins and glial fibrillary acidic protein were assessed immunohistochemically in pituitary adenomas, medullary thyroid carcinomas, endocrine pancreatic tumours, gastric, intestinal and bronchial carcinoids, parathyroid adenomas, pheochromocytomas, paragangliomas and related non-neoplastic tissues. In some cases, immunohistochemical results were correlated with cytoskeletal proteins as analysed by SDS-polyacrylamide gel electrophoresis. Cytokeratin antibodies with broad range of immunoreactivity (i.e. to murine liver cytokeratin component D) reacted with epithelial cells in all non-neoplastic endocrine tissues and related neuroendocrine tumours studied, except for adrenal medulla, pheochromocytoma and paraganglioma, independently of hormone production and biological behaviour. In contrast, antibodies to epidermis-derived cytokeratins failed to stain endocrine tissues and tumours. Paranuclear cytokeratin accumulations were seen in bronchial, gastric, and intestinal carcinoids and seem to be a common feature of neuroendocrine tumours. One-and two-dimensional SDS-polyacrylamide gel electrophoresis of non-neoplastic endocrine tissues and related tumours revealed two major keratin polypeptides corresponding to cytokeratins No. 8 and 18 of the cytokeratin catalog of human cells (Moll et al. 1982). According to this cytokeratin polypeptide composition, endocrine tissues and related tumours conform to the simple type of epithelia. Vimentin-related immunoreactivity was restricted to stromal cells and to folliculo-stellate cells in normal pituitary gland, Schwann cells in carcinoids and satellite cells in normal adrenal medulla and in pheochromocytomas. Neurofilament protein- (70 kD)-antibodies only stained nerve fibers in normal tissues and at the periphery of carcinoid tumour cell complexes, and, to a variable degree, cells in nontumorous adrenal medulla, pheochromocytomas and paragangliomas. Furthermore, neurofilament reactivity was observed along with cytokeratin expression in two bronchial carcinoids.     

Malignant myoepithelioma (myoepithelial carcinoma) of the breast: a detailed cytokeratin study.

AIMS--To study the expression of a range of cytokeratins by malignant myoepithelioma of the breast. METHODS--Immunophenotyping was carried out using a panel of antibodies on paraffin wax embedded and frozen material using immunohistochemistry and double-labelled immunofluorescence. Electron microscopy was also performed. RESULTS--The tumour cells were positive for CAM 5.2, actin, vimentin, and cytokeratin 14 and negative for cytokeratins 18 and 19. Electron microscopy showed well formed desmosomes and hemidesmosomes together with pinocytic vesicles, plentiful rough endoplasmic reticulum and 6 nM microfilaments with focal densities. CONCLUSIONS--The pattern of cytokeratin expression provides further evidence that tumours with a specific myoepithelial phenotype occur rarely in the breast.     

Immunohistochemical demonstration of cytokeratins in endocrine cells of the human pituitary gland and in pituitary,adenomas

Summary Ten non-neoplastic pituitary glands and 22 pituitary adenomas producing different hormones were studied by immunofluorescence microscopy as well as peroxidase-antiperoxidase and biotin-avidin techniques on frozen sections and formalin-fixed, paraffin-embedded material using antibodies to cytokeratin, vimentin, GFAP, neurofilament protein and different pituitary hormones. The endocrine cells in non-neoplastic pituitary glands as well as in most pituitary adenomas were cytokeratin-positive. The cytoplasmic cytokeratin distribution patterns of non-neoplastic and tumor cells were similar and typical of the type of hormone produced: GH-producing normal cells showed a paranuclear condensation of cytokeratin-reactive intermediate filaments; this accumulation was even further accentuated in GH-producing adenomas resulting in fibrous bodies (Kovacs and Horvath 1978) decorated by cytokeratin antibodies. Prolactin-producing cells showed a less intense cytoplasmic cytokeratin-specific staining with focal paranuclear accentuation in non-neoplastic as well as in neoplastic glands. ACTH-producing cells in normal pituitary glands as well as in adenomas exhibited a strong and more uniform cytoplasmic cytokeratin staining. The cytokeratin reactivity in glycoprotein hormone-producing cells of non-neoplastic tissue and adenomas was weak. Vimentin and GFAP reactivity was confined to agranular folliculo-stellate cells. The specific and different distribution patterns of cytokeratins in pituitary cells can, therefore, provide an (indirect) indication to the production of a specific hormone if immunocytochemistry fails to demonstrate hormone production.Dedicated to Prof. Dr. J.H. Holzner on the occasion of his birthday     

Co-expression of four intermediate filament subclasses in childhood glial neoplasms.

Immunohistochemical analysis of intermediate filament (IF) proteins was performed on frozen sections of 16 childhood glial tumors using a library of 10 antigen-specific IF protein directed monoclonal antibodies (MoABs) and a four-step biotin-streptavidin-alkaline phosphatase conjugated antigen detection immunocytochemical technique. Human glial fibrillary acidic protein (GFAP) and vimentin were expressed in all brain tumors. High molecular weight (200 kDa) neurofilament (NF-H) protein was expressed in 15 out of 16 tumors; medium molecular weight (160 kDa) neurofilament (NF-M) in seven out of 16 tumors; and low molecular weight (68 kDa) neurofilament (NF-L) in five out of 16. Positive acidic keratin reactivity was found in five out of 16 tumors using MoAB AE1. Expression of a keratin pair was detected with MoAB AE2 in five out of 16 tumors. A second keratin pair in 14 out of 16 glial tumors was demonstrated with MoAB AE3. Immunostaining with AE5 defined the expression of another basic keratin (64 kDa) in nine out of 16 glial tumors. Finally, in 14 out of 16 astrocytomas an individual 51 kDa acidic keratin (detected with MoAB AE8) was expressed. Glial tumor cells contain cell lineage specific and nonspecific IF proteins in the following IF pattern: AE3+, AE8+, GFAP+, vimentin+, and NF-H+. The heterogenous composition of these cytoskeletal IF proteins in childhood glial tumors may reflect a direct stage dependent correlation with their neoplastic transformation.     

Cytokeratin and neurofilament in lung carcinomas.

Three monoclonal antibodies, one directed against cytokeratin (clone 80) and two directed against neurofilament (clones 2F11 and 3G6), were used in the study of a series of 77 lung carcinomas by immunohistochemical staining. The anti-cytokeratin antibody, a very broadly reacting antibody directed against an antigenic determinant common to a great number of cytokeratins, was applicable on frozen sections. The two anti-neurofilament antibodies, directed against the 70 kD protein (clone 2F11) and the 160 kD and 200 kD proteins (clone 3G6) of neurofilament, were applicable on both frozen sections and paraffin sections. The staining results on the lung carcinomas indicate that all types of tumors studied, including small-cell anaplastic carcinoma, are markedly positive for cytokeratin. Frozen sections of five and formalin-fixed and paraffin-embedded sections of six other small-cell anaplastic carcinomas were negative with both anti-neurofilament monoclonal antibodies. One poorly differentiated squamous cell carcinoma positive with anti-neurofilament clone 2F11 but negative with clone 3G6. This distribution of cytoskeletal proteins demonstrates the epithelial differentiation of all types of lung carcinomas. Neuroendocrine differentiation of lung carcinomas as found in the small-cell anaplastic types does not result in expression of neurofilament proteins.     

Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.     

Basal cell adenocarcinoma of the palate with squamous metaplasia

Basal cell adenocarcinoma is a rare salivary gland tumour, especially in minor glands. The clinical, histological, and immunohistochemical features of a case involving the palate are described. Formalin fixed, paraffin embedded sections of the tumour were examined in haematoxylin and eosin (H&E) sections and also using immunostaining for cytokeratins 7, 8, 13, 14, 18, 19, vimentin, muscle specific actin (HHF35), and laminin. H&E sections showed that the tumour was composed mainly of basaloid cells and a striking feature was the presence of squamous metaplasia. Neural invasion was also conspicuous. Immunohistochemical reactions indicated that cytokeratin 14 was expressed by all tumour cells and vimentin by all cells except those in the areas of squamous metaplasia. The remaining cytokeratins and actin were present in some of the tumour cells, while laminin showed discreet positivity around cell arrangements. The foci of squamous metaplasia and the immunohistochemical findings are helpful in distinguishing basal cell adenocarcinoma from other salivary gland tumours which show basaloid cells.     

Differentiation characteristics of newly established medulloblastoma cell lines (D384 Med, D425 Med, and D458 Med) and their transplantable xenografts

Three new human medulloblastoma (MB) cell lines (D384 Med, D425 Med, and D458 Med) and their transplantable xenografts were examined for antigenic expression with antibodies against neuroectodermal antigens, cytoskeletal proteins, neuroendocrine markers, glioma-associated antigens, tenascin, human lymphocyte antigen molecules, epidermal growth factor receptor, and T-cell antigen by indirect immunofluorescence, avidin-biotin complex peroxidase immunohistochemistry, and immunoblot methods. We found that each of the three cell lines expressed vimentin; low-, middle-, and high-molecular-weight neurofilament proteins; and the synaptic vesicle membrane glycoprotein synaptophysin. Each of the cell lines also reacted with antibodies against neural cell adhesion molecules, but none of them were positive for antibodies against glial fibrillary acidic protein, keratin, microtubule-associated protein tau and microtubule-associated protein 2, human lymphocyte antigen-DR, epidermal growth factor receptor, and T-cell antigen. Immunoreactivities with anti-tenascin and anti-glioma-associated antibodies were variable in these cell lines. Anti-human lymphocyte antigen-A,B and anti-beta 2-microglobulin antibodies reacted with xenografts of D384 Med and D425 Med and were weakly positive for a small population of D384 Med cultured cells. In summary, the detection of neurofilament proteins and synaptophysin and the absence of glial fibrillary acidic protein provide strong evidence for a neuronal phenotype of D384 Med, D425 Med, and D458 Med.     

Antibodies to intermediate filament proteins as molecular markers in clinical tumor pathology. Differentiation of carcinomas by their reaction with different cytokeratin antibodies

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.     

A cytokeratin-immunohistochemical study of hepatoblastoma.

Six cases of hepatoblastoma (five epithelial, one mixed epithelial-mesenchymal) were studied on serially cut cryostat sections, using a panel of monoclonal antibodies directed against individual cytokeratins, vimentin, and desmin, in an indirect immunoperoxidase procedure. Embryonic and fetal-type tumor cells expressed the "hepatocellular" cytokeratins no. 8 and 18 but, surprisingly, also expressed the "bile duct type" cytokeratin no. 19. In addition, two cases had a number of tumor cells which were also positive for the "bile duct type" cytokeratin no. 7. Cells embedded in osteoid-like material were immunoreactive for vimentin but also for cytokeratins no. 7, 18, and 19. Gel electrophoresis, and Western blotting of cytoskeletal extracts, confirmed the immunohistochemical data. The implications of these findings for the histogenesis of hepatoblastoma are discussed in this report.     

Pigmented neuroectodermal tumour of infancy: an immunohistochemical study

The pigmented neuroectodermal tumour of infancy is a rare neoplasm of uncertain histogenesis which, in the majority of cases, arises in the maxilla and pursues a benign course. Currently, it would be classified in the group of peripheral primitive neuroectodermal tumours. Histologically it is composed of two principal cell types: neuroblast-like and melanocyte-like. Three typical cases are presented herein, which appear to be the first examined with a panel of antibodies. The neuroblast-like cells labelled positively for neurone-specific enolase but were negative for S-100, neurofilaments, glial fibrillary acidic protein, vimentin, cytokeratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The melanocyte-like cells stained positively for neurone-specific enolase, vimentin and cytokeratin but were negative for S-100, neurofilaments, glial fibrillary acidic protein, EMA and CEA. The significance of these findings is discussed in the light of previous suggestions about the differentiation that these tumours show.     

Immunohistochemical evidence for mesothelial origin of paratesticular adenomatoid tumour

AIMS: To investigate the histogenesis of paratesticular adenomatoid tumour by use of immunohistochemical markers for a variety of carcinomas and mesothelioma. METHODS AND RESULTS: Immunohistochemical staining of sections from 12 cases of paratesticular adenomatoid tumour was undertaken using primary antibodies to antigens expressed by benign epithelial cells and carcinoma (cytokeratin AE1/AE3, cytokeratin 34ssE12, epithelial membrane antigen, MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1), stromal and vascular markers (vimentin, CD34, factor VIII), and mesothelioma-associated antigens (thrombomodulin, HBME-1, OC 125) and p53 protein. There was absence of immunohistochemical expression of epithelial/carcinoma markers MOC-31, Ber-EP4, CEA, B72.3, LEA.135, Leu M1 and to factor VIII and CD34. All tumours expressed cytokeratin AE1/AE3, epithelial membrane antigen and vimentin, with weak expression of cytokeratin 34ssE12 in 25% of tumours. Each tumour showed expression of thrombomodulin, HBME-1 and OC 125 in a membranous distribution. p53 protein expression was not detected. CONCLUSIONS: The immunohistochemical profile of paratesticular adenomatoid tumour is strongly supportive of a mesothelial cell origin.     

Immunohistochemical analysis of equine pulmonary granular cell tumours

Histopathological and immunohistochemical examinations were made on four female horses aged 9-12 years with pulmonary granular cell tumours (GCTs). The tumours, which were multiple, of varying size, firm and off-white in colour, surrounded the bronchi and bronchioles. Metastatic lesions were not detected. The tumour cells had abundant eosinophilic cytoplasm filled with prominent coarse eosinophilic granules. Immunohistochemically, these tumour cells reacted uniformly with vimentin and S100 antibodies. Most were immunolabelled by antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and protein gene product 9.5 (PGP9.5), and a few cells were positive with Leu7 antibody. However, the tumour cells did not react with antibodies against neurofilament protein (NF), cytokeratin (CK), chromogranin, alpha1 antichymotrypsin (AACT), myoglobin, desmin, alpha-actin or alpha-smooth muscle actin (alpha-SMA). These immunohistochemical properties of tumour cells support the hypothesis that equine pulmonary GCTs are derived from Schwann cells of the peripheral nervous system in peribronchial and peribronchiolar tissues. GFAP, MBP, Leu7 and PGP9.5 antibodies should help to distinguish equine granular cell tumours from other tumours. Copyright Harcourt Publishers Ltd.     

Cytokeratin-specific monoclonal antibodies are reactive with tumours of smooth muscle derivation. An immunocytochemical and biochemical study using antibodies to intermediate filament cytoskeletal proteins

Formalin fixed and paraffin wax embedded tissue from 13 leiomyosarcomas, three leiomyoblastomas, five leiomyomas and fresh tissue from one leiomyosarcoma and one leiomyoma was studied. Tumours were stained by the avidin-biotin-peroxidase technique with antibodies to desmin, vimentin, cytokeratins and S-100 protein. Neoplastic cells in all the cases were positive for desmin and vimentin but were negative for S-100; antibody CAM 5.2 gave strong reactivity with tumour cells of 12 leiomyosarcomas and all leiomyomas, but failed to stain the leiomyoblastomas; LP34 weakly stained two leiomyosarcomas and one leiomyoblastoma. Immunoblot studies using whole cell extracts of one leiomyosarcoma and one leiomyoma respectively, showed 55-58 kd and 35-38 kd bands reactive with monoclonal antibody CAM 5.2. However, no cytokeratin components were demonstrated when cytoskeletal extracts of the same tissue samples were immunoblotted with CAM 5.2. The implications of these findings for the diagnostic histopathologist are discussed.     

Immunohistochemical localization of five classes of intermediate filament in a benign pelvic soft tissue tumor of rhabdoid appearance.

A benign pelvic soft tissue tumor from a 50-year-old woman was examined by immunohistochemistry and electron microscopy. The tumor cells had abundant eosinophilic cytoplasm with a hyaline appearance, which was filled with large aggregates of intermediate-sized filaments (IF). The cells were positively immunostained by antibodies against cytokeratin, vimentin, desmin, glial fibrillary acidic protein, and neurofilament proteins. This case represents an extreme example of the simultaneous expression of IF by neoplastic cells, and exemplifies the limited applicability of immunohistochemical detection of IF antigens for pathological diagnosis of neoplasms.     

Vimentin—a new prognostic parameter in breast carcinoma?

This report describes a positive relationship between vimentin expression in infiltrating ductal breast carcinoma, and high tumour growth fraction. Vimentin expression is potentially a predictor of aggressive behaviour, and such carcinomas may benefit from early adjuvant therapy. Eighty-four malignant breast neoplasms were stained with monoclonal anti-vimentin and anti-cytokeratin antibodies. The tumour growth fractions were determined by immunostaining cryostat sections with the Ki-67 antibody. Seven (9.2 per cent) of 76 infiltrating ductal carcinomas co-expressed cytokeratin and vimentin intermediate filaments in more than 50 per cent of neoplastic cells. In each case, the corresponding Ki-67 count was much greater than 40 per cent, significantly higher than the mean growth fraction for all tumours examined (P less than 0.0001). Vimentin immunoreactivity was also positively related to the histological grade of the ductal carcinomas (P less than 0.002) and inversely related to tumour ER count (P less than 0.0002) and patient age (P less than 0.01). No relationship was observed between vimentin positivity and either the presence of axillary nodal metastases or primary tumour size.