Biomedical subjects
Publications and source records attributed to K C Gatter.
A case is reported of nodular lymphocyte predominant Hodgkin's disease arising 13 years after the removal of a lymph node from the same site which showed marked progressive transformation of germinal centres. The morphological evidence for a histogenetic relationship between the two conditions is presented and discussed.
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Co-expression of intermediate filaments is being increasingly reported for many human tumours including carcinoma of the lung. However, it is unclear whether such findings are unusual or restricted to a group of highly atypical tumours. In the present study the pattern of co-expression of intermediate filaments in 94 human lung tumours has been correlated with light and electron microscopical features which are thought to be atypical for particular tumour types. These same aberrant patterns of intermediate filament co-expression have also been compared with the proliferative rate of these tumours as determined by labelling with the monoclonal antibody Ki67. The results of this study have shown that the aberrant expression of intermediate filaments is not a feature unique to a group of highly unusual tumours but is found throughout the spectrum of lung cancer. The implications of these findings for the use of anti-intermediate filament antibodies in pulmonary pathology are discussed with suggestions for future directions which might be taken in this field.
The monoclonal antibody Ki-1 reacts with Reed-Sternberg cells in Hodgkin's disease and with the tumour cells in a minority of large cell non-Hodgkin's lymphomas. This study describes the results of immunophenotypic and DNA analysis in 30 cases of non-Hodgkin's lymphoma, all of which expressed the Ki-1 antigen. The genotypic analysis has been undertaken using both immunoglobulin and T-cell receptor gene probes. Sixteen cases were shown by this method to be of monoclonal T-cell origin, six of B-cell origin, while in eight cases there was no evidence of either T- or B-cell lineage. This confirms previous immunohistological data indicating that non-Hodgkin's lymphomas which express the Ki-1 antigen may be of either T-cell or B-cell origin.
The monoclonal antibody CAM 5.2 was used to investigate the expression of lower molecular weight cytokeratin proteins immunocytochemically in conventionally processed samples of schistosoma-associated squamous metaplasias and carcinomas of the urinary bladder. The antibody did not differentiate between squamous metaplasias and well differentiated squamous carcinomas, though it did focally label moderate to poorly differentiated tumours. The results suggest that squamous carcinomas of the bladder in this setting differ fundamentally from such tumours at other sites in their patterns of cytokeratin protein expression.
A panel of seven monoclonal antiepithelial antibodies of different specificities, including anticytokeratin, human milk fat globule membrane, C, and carcinoembryonic antigen (CEA) were used with the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique to determine their value in the differentiation between benign and malignant mesothelial cells and lung carcinoma in histological preparations. The anticytokeratin antibody reacted strongly with all cases of reactive mesothelium, mesothelioma, and lung carcinoma. Antibodies to human milk fat globule membrane and the Ca antigen stained mesothelioma and carcinoma and 43% of cases of reactive mesothelium. Staining for carcinoembryonic antigen was not detected in reactive mesothelium or mesothelioma, but was present in most of the lung carcinomas. CEA seemed to be the single most useful marker in distinguishing carcinoma from mesothelioma in that a positive reaction for CEA would indicate carcinoma rather than mesothelioma.
A case of giant cell myocarditis in a patient with non-Hodgkin's lymphoma is reported. To our knowledge, this is a previously unrecorded association and supports the hypothesis that the aetiology of giant cell myocarditis is related to a changed immune state. Immunohistochemical investigation of this case with a panel of monoclonal antibodies against a range of leucocyte and muscle antigens supports the view that the giant cells have a histiocytic rather than a myogenic origin.
A total of 67 samples from normal and pathological thyroid glands were stained (as formalin fixed paraffin sections) with a panel of monoclonal antibodies directed against intermediate filament proteins. The study confirmed previous reports of cytokeratin and vimentin coexpression in primary thyroid carcinomas, but coexpression was also detected in normal thyroid and in a range of benign conditions including follicular adenomas, Hashimoto's thyroiditis, and diffuse hyperplasia (thyrotoxicosis). Prekeratin expression was found (using antibodies recognising higher molecular weight cytokeratins) predominantly in areas of squamous change, independent of the underlying thyroid pathology. This study does not therefore support previous findings that prekeratin expression provides a reliable means of distinguishing follicular pattern papillary carcinoma from follicular carcinoma with its poorer prognosis or that it helps distinguish benign from malignant papillary lesions. No evidence of desmin or neurofilament expression was seen, and in particular, neurofilaments could not be detected in any of the cases of medullary carcinoma studied.
The value of DNA hybridisation (using immunoglobulin and T cell receptor gene probes) was assessed during the diagnosis of problematical lymphoid tissue biopsy specimens. In 14 of 18 specimens (78%), which contained a malignant lymphoproliferation of uncertain aetiology, this technique permitted the demonstration of a monoclonal proliferation of B cells (nine cases) or T cells (five cases). In five further lymph node biopsy specimens, in which the differential diagnosis lay between a reactive or malignant process, a clonal proliferation was shown in three cases. DNA analysis is, therefore, of practical value in resolving many of the diagnostic problems that arise in the assessment of lymphoid tissue biopsy specimens.
This review suggests that immunocytochemistry in diagnostic pathology can be performed using relatively small panels of antibodies and that it should be reserved for situations in which, for one reason or another, the pathologist cannot exert his or her conventional diagnostic skills. Examples include the diagnosis of tumours the true nature of which is uncertain because of anaplasia or poor morphological preservation; the demonstration of small numbers of cells which are otherwise too rare to be recognised in conventionally stained preparations; and the immunophenotyping of non-Hodgkin's lymphomas. Recently progress has been made in the context of non-Hodgkin's lymphomas by the development of monoclonal antibodies that detect T and B cell associated markers in paraffin wax sections. Most of these reagents, however, recognise either lineage associated (but not lineage specific) variants of the leucocyte common antigen CD45, or antigens that are poorly characterised. A recent promising development has therefore been the demonstration that polyclonal antisera raised against the CD3/T3 T cell specific marker (purified by affinity chromatography) are suitable for staining T cells in paraffin sections. This approach will hopefully enable antibodies to be produced which react with other well defined white cell associated markers in routine biopsy material.
Two monoclonal antibodies (To15 and 4KB128) specific for the B cell-associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti-CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti-CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.
The use of monoclonal and polyclonal antibodies for the immunophenotyping of non-Hodgkin's lymphomas in paraffin-embedded tissue has been limited by the fact that most antigens on lymphoid cells are denatured by histologic fixation, dehydration, and embedment. In this article the authors have analyzed a small panel of antibodies which represent exceptions to this rule, in that they identify denaturation-resistant determinants on leukocyte antigens in paraffin-embedded tissue. Monoclonal antibodies L26 [corrected] and 4KB5 label preferentially B cells, monoclonal antibody UCHL1 stains predominantly T cells, and monoclonal antibody MAC 387 reacts with granulocytes and some macrophages. A polyclonal antiserum raised against purified CD3 (T3) antigen, a T-cell-specific molecule, was also employed. This antibody panel was used to immunophenotype routinely processed tissue biopsy specimens from 61 non-Hodgkin's lymphomas (all of which had been previously phenotyped in cryostat sections). The lineage of the neoplastic cells was correctly identified in 32 of 34 (94%) cases of B-cell lymphoma, in 19 of 19 (100%) cases of T-cell neoplasm, and in 2 of 4 (50%) cases of histiocytic malignancy. It is concluded that this combination of antibodies is helpful in immunophenotyping non-Hodgkin's lymphomas when only paraffin-embedded tissue sections are available, although additional reagents of higher specificity are required to improve the identification of lymphomas.
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The origin and mechanism of formation of the osteoclast remains controversial. Although it is known to be derived from a circulating mononuclear percursor, the identity of this cell is unknown. Using a panel of monoclonal antibodies raised against macrophage and other marrow-derived cells, we determined the immunocytochemical staining of human osteoclasts in both fetal bone metaphyseal imprints and frozen sections. Osteoclasts and marrow mononuclear cells were stained by three broad spectrum antimacrophage antibodies, EBM-11, Y182a and BM2. T310, an antibody which stains macrophages and T helper cells, and C17, an antimegakaryocyte antibody, also stained osteoclasts. EBM-11, Y182a and BM2 also stained megakaryocytes in bone imprints as well as normal bone marrow smears. The presence of macrophage-associated antigens in osteoclasts, megakaryocytes and bone marrow mononuclear cells indicates that they are phenotypically similar to macrophages.
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In a previous paper from this laboratory, the production of monoclonal antibodies recognizing antigenic determinants common to the alpha and beta chains of bovine brain S-100 protein was reported. In the present study, the immunohistochemical labeling patterns of these monoclonal antibodies against a wide range of normal and pathologic human tissues are described, and these results are compared with those obtained using polyclonal anti-S-100 antiserum. Although many of the reactions of the monoclonal antibodies were very similar to those of the polyclonal antiserum (and the previously reported sites of S-100 immunoreactivity) several additional cell types (e.g., thyroid follicular cells, biliary epithelium, pancreatic cells, renal tubules) were labeled by one or both of the monoclonal antibodies. Blocking experiments prove that immunohistochemical differences obtained with monoclonal and polyclonal antibodies are at least partly caused by differences in the repertoire of antigenic determinants on S-100 protein that are recognized by the two species (i.e., mouse and rabbit, respectively). These results indicate that S-100 may be more widespread in human tissues than previously thought, and that its value as a marker of the histogenetic origin of human tumors should be reappraised. It is suggested that the marked variability observed in the reactivity of different tissues in the present study may indicate that S-100 is a heterogeneous group of molecules, and its expression may be related to the functional activity of cells.