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Biomedical subjects

K C Gatter

Publications and source records attributed to K C Gatter.

At least 271 records · Page 15Linked to original sources

T-helper cell lymphoma involving the lymph nodes and skin. A clinical, morphologic, and immunohistochemical analysis of five cases.

The clinical, morphologic, and immunohistochemical features of 5 cases of peripheral T-cell lymphoma with lymph node and skin involvement are reported. All patients were male and presented with generalized lymphadenopathy and skin lesions. Lymph node biopsy specimens showed a diffusely growing, pleomorphic, atypical lymphoid infiltrate composed of markedly irregular small and large cells. The stroma consisted of plasma cells, eosinophils, epithelioid histiocytes, and an increased number of small blood vessels. A similar neoplastic infiltrate was observed in the cutaneous nodules that developed in three patients. Immunohistochemistry on frozen tissue sections of lymph nodes using a broad panel of monoclonal antibodies revealed that the neoplastic cells were reactive with anti-T-cell antibodies, the majority of them belonging to the helper/inducer T-cell subset. Stromal plasma cells contained polyclonal immunoglobulins. It is concluded that the malignant lymphoma of peripheral helper/inducer T-cell origin observed in these five patients represents a variant of a mixed, blastic/cell T-cell lymphoma, characterized by a peculiar stromal component and skin involvement.

Aged↗

An immunohistological study of giant-cell tumour of bone: evidence for an osteoclast origin of the giant cells.

Using a panel of monoclonal antibodies against a variety of lymphoid and non-lymphoid antigens the immunohistological staining pattern of giant cells from a case of giant-cell tumour of bone has been compared with that of osteoclasts from the developing ends of fetal long bones. Only EBM-11, an antibody reacting with a wide spectrum of macrophages, stained both osteoclasts and giant cells; stromal cells and osteoblasts did not react. This indicates that osteoclasts and giant cells are phenotypically and presumably functionally similar. It is argued that the osteoclasts and the tumour-derived giant cells in bone are derived from a similar mononuclear precursor.

Adult↗

Immunohistologic demonstration of abnormal colonic crypt cell kinetics in ulcerative colitis.

A monoclonal antibody, Ki-67, that reacts with cells in the proliferative phases (G1, G2, S, and M) of the cell cycle was used in an immunohistochemical labeling reaction to examine the colonic crypt epithelium in active ulcerative colitis, inactive ulcerative colitis, and normal mucosa. The proportions of labeled cells in the lower two thirds (proliferative zone) and in the upper quarter of the crypt were determined. The proportions of Ki-67-positive crypt epithelial cells in both the proliferative zone and the upper crypt were higher in biopsy specimens from patients with active ulcerative colitis than from patients with normal mucosa or with inactive ulcerative colitis. In inactive ulcerative colitis the proportion of Ki-67-positive epithelial cells in the proliferative zone of the crypt was higher than in normal mucosa. These results are similar to those obtained in studies using tritiated thymidine to determine the proportion of cells in the DNA-synthesizing thymidine to determine the proportion of cells in the DNA-synthesizing phase of the cell cycle and suggest that immuno-histochemical staining with Ki-67 may be a practical method for measuring the proliferative activity of epithelial cells in patients with ulcerative colitis and other disorders of the gastrointestinal tract.

Antibodies, Monoclonal↗

The value of immunocytochemical methods in the differential diagnosis of anaplastic thyroid tumours.

The practical usefulness of a panel of monoclonal antibodies recognising epithelial and lymphoid antigens has been evaluated on a series of 10 routinely processed thyroid tumours of uncertain origin. All 6 small cell tumours were shown to be of lymphoid origin whereas of the 4 large cell tumours two were lymphomas and two carcinomas. Two of the tumours, one large cell and one small cell, were undiagnosable due to technical reasons (crush artefact or small size of biopsy) and emphasized the value of immunohistology in this context. Clinical follow-up of all 10 cases indicated that these distinctions are of both prognostic and therapeutic value. It is concluded that immunocytochemistry using a carefully selected panel of monoclonal antibodies is a valuable and convenient means of making an objective distinction between anaplastic thyroid tumours of epithelial or lymphoid origin.

Aged↗

Production of monoclonal antibodies against human epithelial membrane antigen for use in diagnostic immunocytochemistry.

Two monoclonal murine antibodies have been raised against a delipidated extract of human cream. These antibodies were detected by immunohistological screening of hybridoma culture supernatants on sections of human breast tissue. One of those antibodies (E29) was subsequently screened against a range of normal and neoplastic human tissues and shown to react with a wide variety of human epithelia and with mesothelial cells. Antibody E29 was unreactive with other cell types, with the exception of occasional plasma cells. Antibody E29 is suitable for use on paraffin embedded tissue and represents a valuable reagent for the identification of tumours of epithelial origin.

Animals↗

The differential diagnosis of hairy cell leukemia with a panel of monoclonal antibodies.

A panel of monoclonal antibodies reactive with normal human lymphoid cells and with hairy cells has been applied to the immunocytochemical analysis of hairy cell leukemia. Staining was performed by immunoenzymatic methods on frozen sections of bone marrow trephines and extramedullary tissues and on cell smears. Hairy cells reacted with antibodies against HLA-DR, leukocyte common antigen, B-cell antigens (antibodies To15 and B1) and with three anti-hairy cell monoclonal antibodies (S-HCL3, HC1, and HC2). Neoplastic cells in other B-cell lymphoproliferative disorders also expressed HLA-DR, leukocyte common, and B-cell antigens but were consistently negative for the antigen detected by monoclonal antibody S-HCL3. Furthermore, hairy cells differed from other neoplastic B-cells in that they were unreactive with monoclonal antibodies against C3b receptors, anti-Leu-1, Tü1, Tü33, and lacked a meshwork of dendritic reticulum cells. These findings establish a distinctive antigenic phenotype for hairy cell leukemia and indicate that it may be diagnosed reliably by immunoenzymatic labeling of tissue sections or cell smears.

Acute Disease↗

Human lung tumours: a correlation of antigenic profile with histological type.

Fifty-four human lung tumours have been immunostained with a large panel of monoclonal antibodies including reagents against cytokeratins, prekeratins, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and neural antigens. These results have been compared with the histological types of tumour using the current WHO classification scheme. The most striking finding of this study was the considerable overlap of antigenic profile between different histological types of tumour. This suggests that there may be a greater underlying similarity between different histological categories of lung tumour than has hitherto been assumed. Secondly it was evident that immunostaining highlighted areas of different morphology within many tumours emphasizing the heterogeneous differentiation patterns seen in lung cancers. The present study supports the viewpoint that lung tumours arise from a common stem cell and that these neoplasms represent a single tumour with a tendency to differentiate along one or more pathways.

Antibodies, Monoclonal↗

The characterization of two monoclonal anti-keratin antibodies and their use in the study of epithelial disorders.

The present paper describes the production and characterization of two monoclonal antibodies, K20 and K92. Immunohistological staining showed these two antibodies to be specific for keratinizing epithelium. However, whereas K20 stained all layers of the epidermis K92 reacted with only the suprabasal epidermal layers. Immunoblotting studies with preparations of keratins from both the non-cornified (i.e. the basal, spinous and granular layers) and cornified (stratum corneum) layers of epidermis showed that K20 recognized the 46, 48, 50, 55, 56, 56.5, 59, 61, 62, 64, 65, 66 and 67 kd bands, of which the 50 and 46 kd bands appeared to be masked in tissue sections. In contrast, antibody K92 was more restricted in its activity, recognizing only the 55 and 56 kd bands strongly. These antibodies were used in the study of various epithelial disorders and revealed alterations in the epithelial intermediate filament expression in both benign and malignant disease processes.

Animals↗

An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumours.

A series of 41 fresh and 36 routinely processed malignant melanomas were immunostained with a panel of 12 monoclonal antibodies reactive against a range of epithelial, lymphoid, and melanoma associated antigens. The aim of the study was to determine whether this panel of antibodies would be useful in diagnostically difficult cases for differentiating melanomas from other tumours, particularly carcinomas and lymphomas. The results confirmed that most unequivocal malignant melanomas can be identified by positivity for S100 protein and for the antigen recognised by antibody NK1/C3, and by negativity for epithelial and lymphoid antigens. The incidence of melanomas expressing cytokeratin antigens was higher, however, particularly in cryostat sections than has previously been reported. It is therefore suggested that a panel of antibodies with more than one marker in each category should be used for identifying melanomas in clinical practice.

Antibodies, Monoclonal↗

Giant cell myocarditis: evidence for the macrophage origin of the giant cells.

In order to elucidate the origin of giant cells in giant cell myocarditis a case has been studied immunohistologically using monoclonal antibodies against a variety of antigens, including those associated with muscle and macrophages. The results strongly suggest that the giant cells are derived from macrophages rather than the muscle cells.

Adult↗

Role of immunohistochemistry in diagnosis of nasopharyngeal tumours.

To evaluate the usefulness of immunocytochemistry in the differential diagnosis of nasopharyngeal tumours, 35 undifferentiated nasal carcinomas were examined with a panel of monoclonal antibodies against a wide variety of epithelial and non-epithelial antigens. The results were compared with those obtained from a series of nasopharyngeal tumours comprising three squamous cell carcinomas, six lymphomas, one rhabdomyosarcoma, and one yolk sac tumour. All of the carcinomas were positive with at least one of the antiepithelial markers and negative for the leucocyte common antigen and were clearly distinguishable from the nasopharyngeal lymphomas, which gave the opposite staining pattern. It was concluded that such a panel of monoclonal antibodies would be extremely useful for the differential diagnosis of nasopharyngeal tumours, particularly with small or technically inadequate biopsies.

Antibodies, Monoclonal↗

Human lymphoid cells express epithelial membrane antigen. Implications for diagnosis of human neoplasms.

Epithelial membrane antigen (EMA) is generally assumed to be expressed only on epithelial cells. However, EMA was also found on reactive and neoplastic plasma cells, on some non-Hodgkin's lymphomas (particularly cases of T-cell lymphoma and "malignant histiocytosis"), and on Reed-Sternberg cells in cases of lymphocyte-predominant Hodgkin's disease. EMA was also induced on normal blood lymphocytes by exposure to human T-lymphotropic virus type II or phytohaemagglutinin. The specificity of these aberrant reactions was confirmed by the use of three different monoclonal anti-EMA antibodies (E29, HMFG2, and LICR.LON/M8), and by showing that EMA in lymphoid tissue is similar in molecular weight to EMA in human milk. These results indicate that additional anti-epithelial antibodies (eg, anti-cytokeratins) should be used in conjunction with anti-EMA for tumour diagnosis.

Antibodies, Monoclonal↗

Freeze-dried paraffin-embedded human tissue for antigen labelling with monoclonal antibodies.

Conventional fixation and paraffin embedding of human tissue destroys most of the antigens detected with currently available antibodies, while cryostat sections give poor morphological detail and require freezer space for storage. However, when tissue was freeze-dried before being embedded in paraffin S then stained for a wide range of antigens recognised by monoclonal antibodies (including T-cell and B-cell antigens), morphological preservation was clearly better, and the labelling reactions were of equal (or greater) intensity, than with cryostat sections. As the number of diagnostically important monoclonal antibodies continues to increase the use of freeze-dried paraffin sections should facilitate the introduction of immunohistological techniques for both routine histopathological diagnostic work and immunological research.

Antibodies, Monoclonal↗

The immunocytochemical detection of axillary micrometastases in breast cancer.

The histological detection of tumour metastases in axillary lymph nodes from cases of breast carcinoma is of major prognostic significance, but may be difficult when metastases are of microscopic size. We have therefore investigated whether immunohistological techniques can increase the accuracy of metastasis detection in axillary lymph nodes. Forty-five cases of breast carcinoma were studied, in all of whom the axillary lymph nodes had been reported as free of metastases. Paraffin sections from these cases were stained by immunoenzymatic techniques, using monoclonal antibodies directed against human milk fat globule membrane antigen ("anti-EMA") and against epithelial intermediate filaments ("anti-keratin"). In 4/12 cases of lobular carcinoma and in 3/33 cases of ductal carcinoma, previously unsuspected micrometastases were revealed by immunohistological staining, representing an overall increase in detection rate of 15% (and of 33% for the lobular carcinoma cases). In addition to this group of 45 histologically "negative" biopsies, 12 samples were studied in which only a proportion of the nodes had been reported as containing tumour. In 5 of these cases immunostaining revealed previously undetected metastases. These findings suggest that immunohistological analysis may have a routine role to play in the staging of breast carcinoma. It is noted that the 15% increase in diagnostic accuracy achieved in the present study is comparable to the proportion of breast carcinoma patients in whom disseminated disease develops despite their axillary lymph nodes being reported as tumour-free at the time of surgery.

Alkaline Phosphatase↗

An immunohistological study of testicular germ cell tumours using two different monoclonal antibodies against placental alkaline phosphatase.

Using two monoclonal antibodies directed against placental alkaline phosphatase (H17E2 and D20L) the immunohistological staining of testicular germ cell tumours was compared with that of a wide range of normal and malignant tissues. All seminomas and malignant teratomas tested gave strong positive labelling with H17E2 but were either negative or only patchily positive with D20L. Neither antibody gave any positive reaction on the normal tissues tested. All other malignancies were negative with both antibodies apart from two cases of ovarian and one case of endometrical cancer (strongly stained by H17E2) and three cases of colonic carcinoma (weakly and patchily stained by both H17E2 and D20L). This indicates that germ cell neoplasms generally express a form of placental alkaline phosphatase recognised by antibody H17E2.

Alkaline Phosphatase↗

The differential diagnosis of routinely processed anaplastic tumors using monoclonal antibodies.

The value of immunohistological labeling with a panel of monoclonal antibodies in the diagnosis of routinely processed surgical biopsies has been assessed. The cases examined consisted of an unselected series of tumor biopsies referred during a 12-month period because of doubt as to the nature of the neoplasm and are representative of the type of diagnostic problem regularly encountered in routine surgical pathology. In 30 of the 38 cases studied, reactivity with monoclonal antileukocyte antibody (and nonreactivity with monoclonal antiepithelial antibodies) indicated that the tumor was a lymphoma. Seven of the remaining eight cases gave the reverse reaction pattern and therefore were classified as carcinomas, while one biopsy was unreactive with all antibodies. Review of the clinical details in each case showed that the clinical management in several instances was influenced by establishing the correct diagnosis and it therefore is suggested that immunohistologic examination should be used more widely in the study of tumors that give rise to diagnostic difficulty.

Aged↗

Immunohistological analysis of human bone marrow trephine biopsies using monoclonal antibodies.

This paper describes the use of a recently developed immuno-alkaline phosphatase method (the 'APAAP' technique) for labelling frozen sections of undecalcified bone marrow biopsies with monoclonal antibodies, including reagents reactive with T cells and their subsets, B cells, glycophorin, HLA-DR antigen, common ALL antigen, epithelial cells and megakaryocytes. Use of an immuno-alkaline phosphatase technique avoids problems due to endogenous enzyme activity encountered when staining bone marrow by immunoperoxidase procedures. Immunohistological labelling of frozen trephine biopsies is of particular value when it is impossible to aspirate marrow particles and for identifying cells which do not readily enter suspension (e.g. dendritic reticulum cells or stromal cells). Details are given of cases in which immunohistological analysis was used for the phenotyping of acute leukaemias, for the differential diagnosis of intramedullary T and B cell proliferations, and for identifying bone marrow metastases.

Alkaline Phosphatase↗

An immunohistological study of the cellular constituents of Hodgkin's disease using a monoclonal antibody panel.

Cryostat sections of lymphoid tissue from 44 cases of Hodgkin's disease were analysed by immunoperoxidase staining using a panel of monoclonal antibodies which included reagents reactive with T cells and their subsets, B cells, HLA-DR, Ig, dendritic reticulum cells and C3b receptor. A wide spectrum of immunohistological patterns was observed ranging from cases in which T cells were numerous (B cells being absent or present in only small numbers) to cases in which very prominent B cell follicles were present. These follicles contained a meshwork of dendritic reticulum cells and were composed of polyclonal B cells (as assessed by light chain expression). T cells were present in small numbers within these B cell follicles, often clustered in a thin rim around individual Reed-Sternberg and Hodgkin's cells. All B cell-rich cases were examples of lymphocyte predominant Hodgkin's disease. Assessment of the T cell helper/suppressor ratios was hindered by the fact that both anti-helper antibodies (OKT4 and anti-Leu 3a) reacted with macrophages. However the majority of cases appeared to contain a normal excess of T helper cells. HLA-DR was strongly expressed in T cell rich areas, on Reed-Sternberg and Hodgkin's cells, on vascular endothelium and on numerous infiltrating cells in the fibrous tissue areas in cases of nodular sclerosing disease. Reed-Sternberg and Hodgkin's cells were not labelled by either anti-fibronectin or by antibodies reactive with dendritic reticulum cells (anti-C3b receptor and antibody R4/23).

Antibodies, Monoclonal↗