Limitations encountered in the application of tissue section immunodiagnosis to the study of lymphomas and related disorders.
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Antibodies, Monoclonal↗
Biomedical subjects
R V Rouse
Publications and source records attributed to R V Rouse.
Monoclonal anti-keratin (AE1) reactivity in routinely processed tissue from 166 human neoplasms.
A large number of human neoplasms were tested for their keratin expression in routinely processed tissues by a simple, three-stage immunoperoxidase method using a broadly reactive monoclonal anti-keratin antibody AE1, which recognizes a number of keratin polypeptides distributed in a wide variety of epithelia. All carcinomas, with the exception of hepatocellular, adrenocortical, and basal cell carcinomas and occasional renal cell, pulmonary small-cell, and pulmonary large-cell anaplastic carcinomas, reacted with this antibody irrespective of differentiation, in most instances displaying staining of strong or moderate intensity in the majority of tumor cells. Equivocal results were obtained in some seminomas and dysgerminomas. Malignant melanoma, large-cell lymphoma, Hodgkin's disease, malignant histiocytosis, and stromal mesenchymal elements in all tumors did not show any reactivity with AE1. Even after routine processing, the determinant detected by AE1 is conserved and restricted to epithelial neoplasms. This suggests that AE1 would be valuable in the diagnostic distinction of anaplastic carcinoma from lymphoma and melanoma in routinely processed tissues.
Antibodies, Monoclonal↗
Prostatic adenocarcinoma with endometrioid features. Clinical, pathologic, and ultrastructural findings.
Thirteen cases of prostatic adenocarcinoma with endometrioid features were reviewed. The patients were older men (49-81 years) presenting with symptoms of hematuria and urinary obstruction. Each of the tumors displayed exophytic growth into the prostatic urethra, with involvement of the verumontanum. The urethral orifices of the large (primary) prostatic ducts were uniformly involved, and coexistent invasive (acinar) adenocarcinoma was identified in 10 cases (77%). The tumors exhibited a complex glandular pattern strikingly similar to uterine endometrial carcinoma, with prominent papillary formation in six cases. All cases demonstrated intense cytoplasmic immunoreactivity for prostatic acid phosphatase and prostate-specific antigen in at least part of the tumor. Focal staining for carcinoembryonic antigen was seen in three cases. Five tumors examined ultrastructurally demonstrated typical features of prostatic adenocarcinoma. Follow-up information was available on all 13 patients (6-83 months). Seven patients died of metastatic tumor (9-70 months after diagnosis), and the other six patients exhibited recurrent local or metastatic tumor. The sites of metastases were identical to those seen with invasive "acinar" prostatic adenocarcinoma, including pelvic lymph nodes, bones, and lungs. Crude 5-year survival was 15%, with a mean survival of 37 months. Adjuvant therapy provided palliative relief for many patients, but did not appear to influence survival. These findings indicate that endometrioid carcinoma is a histologically distinct variant of prostatic adenocarcinoma, with a more aggressive clinical behavior than previously thought.
Adenocarcinoma↗
Expression of major histocompatibility complex antigens in the thymuses of chimeric mice.
Thymuses of various types of bone-marrow-chimeric mice have been examined by tissue section immunologic staining for the presence and distribution of major histocompatibility complex (MHC) antigens. Cortical and medullary thymic epithelial cells continue to express thymus genotype I-A and H-2K/D antigens for at least 6 months posttransplantation. The appearance of bone-marrow-type MHC antigens is limited to low levels of H-2K/D on cortical and medullary lymphocytes, and to dendritic cells in the medulla; the medullary dendritic cells express high levels of donor-type I-A antigens as soon as 3 weeks posttransplantation. The observed patterns support the concept that I-A antigens are synthesized by thymic epithelial cells but are acquired by thymocytes. The findings are of relevance to the understanding of the role of the thymus in the generation of MHC restriction.
Animals↗
Morphologic and immunologic characterization of 50 peripheral T-cell lymphomas.
Fifty T-cell lymphomas, excluding mycosis fungoides and lymphoblastic lymphoma, were studied morphologically and immunohistochemically with a panel of monoclonal antibodies reactive with T-cell differentiation antigens in fresh frozen tissue. Histologically, 36% of the lymphomas were large-cell immunoblastic, 26% were diffuse large-cell, 22% were diffuse mixed small and large-cell, and 16% were monomorphic medium-sized-cell lymphomas. By immunologic studies, 64% of the lymphomas were of helper phenotype, 12% were of cytotoxic/suppressor phenotype, 8% expressed both helper and cytotoxic/suppressor suppressor antigenic markers, and 16% lacked detectable markers for either helper or cytotoxic/suppressor cells. There was no correlation between histologic category and immunophenotype. A common finding, and one which may prove to be helpful in the diagnosis of T-cell lymphomas, was the loss of one or more of the pan-T antigens Leu 1, 4, and 5 or the T-cell antigen Leu 9 in 32 cases. The expression of Leu 1 and Leu 9 was lost in 46% of cases, expression of Leu 4 was lost in 26%, and expression of Leu 5 was lost in 24%. About three-quarters of the lymphomas expressed Ia antigens.
Antibodies, Monoclonal↗
Localization of lymphocyte subpopulations in peripheral lymphoid organs: directed lymphocyte migration and segregation into specific microenvironments.
The distribution of lymphocytes in the peripheral lymphoid organs is controlled by recirculatory and microenvironmental factors. Specific interactions between recirculating lymphocytes and high endothelial venules in various lymphoid organs determine the presence and proportions of the various lymphoid sets and subsets in those organs. Separate endothelial determinants on peripheral node and Peyer's patch endothelium along with complementary lymphocyte receptors mediate this organ specificity. B and T cells also exhibit nonrandom organization within lymphoid tissues; after entry via high endothelial venules they segregate into their respective domains, which appear to be determined by distinct types of nonlymphoid stromal cells. Antigenic stimulation results in changes in lymphocyte phenotype as well as in the lymphoid microenvironment. The response to most complex antigens is the formation of germinal centers (GC) composed primarily of proliferating B cells; the phenotype of the few T cells therein is supportive of the GC as a site of B-T interaction. The phenotype of the B cells in GCs suggest a role for GCs in immunoglobulin class switching and the determination of subsequent homing specificity.
Animals↗
The extent of surgery after chemotherapy for advanced germ cell tumors.
The histopathological findings of tissue removed from 40 patients with a residual mass after completion of induction chemotherapy with cis-platinum, vinblastine and bleomycin are reviewed. These patients with advanced testicular cancer were treated with chemotherapy until normalization of tumor markers and until there was no further decrease in the size of palpable or radiologically evident masses for 2 successive cycles of chemotherapy. The mean number of chemotherapy cycles preoperatively was 5.2. Residual carcinoma was found in only 1 patient (3 per cent), teratoma in 18 (45 per cent), and fibrotic and/or necrotic masses in 21 (52 per cent). With this tailored treatment regimen in which an operation is performed after maximal chemotherapeutic response, the number of patients with viable residual tumor at operation can be minimized. Complete retroperitoneal lymph node dissection concomitant with resection of the residual mass was performed in 22 of 32 patients with residual masses in the retroperitoneum. The 1 patient with carcinoma in the mass also had carcinoma in several of the lymph nodes, and 4 of the 11 with teratoma in the mass had teratoma in the lymph nodes. Since the histopathological findings of the mass often parallel those of the lymph nodes, and since masses containing only fibrosis and/or necrosis cannot be ascertained with accuracy at operation, a complete retroperitoneal lymph node dissection is recommended in patients with a residual retroperitoneal mass.
Adolescent↗
Expression of a T-cell antigen (Leu-1) by B-cell lymphomas.
The Leu-1 antigen has been defined by monoclonal antibodies (L17F12, T101, and OKT-1) as a pan-T-cell antigen present on all human peripheral blood T cells and thymocytes. Although originally thought to be confined to T-cell lineage, some cases of B-cell chronic lymphocytic leukemia have been found to react with these antibodies. Using a frozen section immunoperoxidase staining technique, 125 lymphomas with B-cell differentiation were examined for the presence of Leu-1 antigen. Leu-1 antigen was detected in 4 of 11 cases of diffuse small lymphocytic lymphoma (Rappaport's DWDL) and 3 of 4 cases of diffuse intermediate lymphocytic lymphoma. Follicular lymphomas less often expressed this antigen--2 of 29 cases of the small cleaved cell type (Rappaport's NPDL), none of 13 cases of mixed small cleaved and large cell type (Rappaport's NM), and 1 of 6 cases of large cell type (Rappaport's NH). Diffuse lymphomas of presumed follicular center cell origin expressed this antigen infrequently as well--1 of 3 cases of the small cleaved cell type (Rappaport's DPDL), neither of 2 cases of mixed small cleaved and large cell type (Rappaport's DM), and 3 of 43 of large cell type (cleaved/noncleaved) (Rappaport's DH). Diffuse large cell, immunoblastic lymphoma of B-cell type expressed Leu-1 in 1 of 6 cases. None of the 3 cases of Burkitt's lymphoma or of the three small noncleaved non-Burkitt's lymphoma (Rappaport's undifferentiated) expressed detectable Leu-1. B-lymphoblastic lymphoma (1 case) and B-cell unclassified lymphoma (1 case) both failed to express detectable Leu-1. It appears that this pan-T-cell antigen is mainly found on those B-cell lymphomas composed predominantly of small lymphocytes. This finding may be of use in distinguishing extranodal neoplastic collections of small lymphocytes from lymphocytic hyperplasias.
Antibodies, Monoclonal↗
Expression of T cell antigens by cells in mouse and human primary and secondary follicles.
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Animals↗
The principal cells in the thymus expressing MHC antigens are epithelial.
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Animals↗
Expression of HLA antigens by human thymic epithelial cells.
Human thymuses were examined by tissue section staining with antibodies specific for monomorphic and polymorphic HLA-A, B, C, and DR determinants. The principal cell type expressing high levels of HLA antigens has the distribution of epithelial cells. Immunoelectron microscopy confirmed their epithelial nature. As in the mouse, both medullary and cortical epithelial cells express high levels of class II (DR) antigens, a finding that is remarkable in that these antigens were originally thought to be restricted to lymphoid and accessory cells. Class I (A, B, and C) antigens are also present on thymic epithelial cells. They are easily detectable on medullary epithelial cells, but two distinct patterns of cortical staining were observed. One group of antibodies produced intense dendritic staining throughout the cortex; the other group produced only faint or no cortical dendritic staining at all. These different staining patterns do not correlate with known properties of the antibodies and thus appear to be due to intrinsic properties of the different A, B, and C antigens.
Adult↗
Thymocyte rosettes: multicellular complexes of lymphocytes and bone marrow-derived stromal cells in the mouse thymus.
We describe the isolation and purification of multicellular complexes composed of lymphocytes and bone marrow-derived stromal cells ("thymocyte rosettes") from the mouse thymus. These rosettes are the structural in vitro correlate of in vivo associations between lymphoblasts and I-A/E negative macrophages or medullary I-A/E positive dendritic-like cells. Both types of rosettes are preformed in vivo. The rosette-associated thymocytes display a surface antigen phenotype typical of immature thymocytes. In radiation chimeras, replacement of host thymocytes by injected bone marrow cells follows a regular pattern: donor type T cells appear first at day 11 as clusters around I-A negative macrophages and approximately 2 days later as similar clusters associated with either I-A positive cortical epithelial cells or I-A positive medullary dendritic cells. These data suggest (a) a defined sequence of lymphostromal interactions during intrathymic maturation and (b) a rapid proliferation of thymocytes after interaction with stromal cells.
Animals↗
Human prostate specific and shared differentiation antigens defined by monoclonal antibodies.
Splenic lymphocytes of BALB/c mice immunized with membrane-enriched fractions of human benign prostatic hyperplasia tissues were fused with the NS-1 light chain-secreting murine myeloma cell line. This generated hybridoma cultures that secreted immunoglobulins reactive in solid-phase radioimmunoassays with membrane preparations of prostatic tissues but not with membrane preparations of apparently normal human liver, spleen, thymus, or erythrocytes. After further screening of immunoglobulin reactivities and cloning of cultures, eight monoclonal antibodies were chosen that demonstrated reactivity with human prostate tissues. These monoclonal antibodies could be placed into at least three major groups--epithelium-specific, polyepithelial, and stroma-specific--on the basis of differential binding to the surfaces of various component cells in the prostate and other epithelia. Two antibodies defined unique protein antigens specific for prostate epithelia that were not crossreactive with prostatic acid phosphatase or the recently described "prostatic antigens." These antibodies also detected antigens on malignant prostate tissues as well as other malignant tissues. Four antibodies defined three unique polyepithelial protein antigens (two of the antibodies were different isotypes defining the same protein). Each of the polyepithelial antigens was expressed on a different spectrum of normal epithelial tissues. Two displayed brain tissue crossreactivity, one was present on pancreas, and one was present on platelets. The two antibodies that detected prostatic stromal protein antigens showed different spectra of reactivities. One antibody reacted with apparently all prostatic stromal cells as well as endothelial cells in the prostate and other organs. The other antibody apparently reacted with all prostatic stromal cells as well as myoepithelial and muscle cells in other organs.
Antibodies, Monoclonal↗
Mouse lymph node germinal centers contain a selected subset of T cells--the helper phenotype.
Cells staining for Lyt-1 are more frequent than cells staining for Lyt-2 in both primary follicles and the cuffs of secondary follicles; there is an even more striking predominance of cells bearing only Lyt-1 in germinal centers. In addition, there is an increase in the total percentage of cells bearing T cell antigens in germinal centers compared to primary follicles. These differences in phenotype and distribution of T cell populations indicate the T cells in B cell areas, and especially in germinal centers, are not randomly selected, but rather represent a specific subpopulation of T cells enriched for the helper phenotype (Lyt-1+2-), perhaps involved in the development and/or function of germinal centers.
Animals↗
Monoclonal antibodies to a human prostate antigen.
Three monoclonal antibodies reactive with a purified extractable Mr 34,000 prostate antigen (PA) have been prepared by fusing splenocytes of BALB/c mice preimmunized with purified PA with the NS1 mouse myeloma cell line. The three antibodies were all of the IgG-1 subclass. The antibodies defined two noncross-blocking unique determinants on PA; each present as one site per molecule. IF3 defined one antigenic site and 2G7 and 1C5 defined another antigenic determinant. All of the antibodies reacted with PA in a solid-phase radioimmunoassay and immunoprecipitated 125I-labeled PA. Absorption and sandwich radioimmunoassays showed PA in prostate tissues but not in tonsil, liver, or kidney. Immunoperoxidase staining of formalin-fixed paraffin-embedded sections of benign prostatic hyperplasia and prostatic carcinoma revealed strong prostate epithelial reactivity. None of the antibodies showed reactivity with prostate membrane preparations. A sandwich radioimmunoassay used 2G7 as a plate coat. 125I-labeled 1F3 was used to detect 5 ng PA per ml in sera of patients with prostate cancer. These results confirm previous observations regarding the specificity of PA and shed new evidence for its intracellular localization.
Antibodies, Monoclonal↗
Identification of T cell subsets and B lymphocytes in mouse brain experimental allergic encephalitis lesions.
Tissue section immunoperoxidase staining, employing monoclonal antibodies specific for T cell antigens (Lyt-1, Lyt-2) and B cells (B220), was used to study the brains of mice with experimental allergic encephalitis. Cells bearing phenotypes characteristic of both helper (Lyt-1+2-) and cytotoxic/suppressor (or precursor) (Lyt-2+) T cells, as well as B cells, are present in the perivascular cuffs in brains of EAE mice during active disease and the recovery phase. Lyt-1+ cells comprise 49% of the inflammatory cell population, and Lyt-2+ and B220+ cells are found at frequencies of 10% and 12%, respectively.
Animals↗
Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation.
The surface phenotype of Peyer's patch germinal center lymphoid cells in the mouse is described. It is confirmed that most germinal center lymphocytes bind high levels of peanut agglutination (PNA), a lectin with specificity for terminal galactosyl residues. It is shown that germinal center lymphocytes can be identified in cell suspensions as a discrete PNAhi population distinct from other B cells, plasma cells, and most T cells, which bind only low levels of PNA. Using fluorescence-labeled PNA as a marker in dual fluorescence studies, we found that the majority of Peyer's patch germinal center cells are B lymphocytes: PNAhi Peyer's patch cells express B220, the B lineage-specific form of the T200 family of molecules, as well as low levels of surface Ig. They do not express the T cell-lineage antigens Thy-1, Lyt-1, or Lyt-2 (only 1 to 3% positive). They bear lower levels of H2-K than PNAlo B cells, but two to three times the level of surface I-A-encoded determinants. A discrete but variable subpopulation of PNAhi Peyer's patch cells bear ThB in AKR/c mice, but BALB/c PNAhi lymphocytes are ThB-. About 10 to 30% bear surface IgM or IgG, but in contrast to essentially all PNAlo B lymphocytes in this site, they express no detectable surface IgD. The majority of Peyer's patch germinal center cells bear surface IgA, and this IgA is allelically excluded in F1 mice, indicating it is synthesized by the germinal center cells themselves. In fact, germinal centers contain most of the IgA-bearing cells in Peyer's patches (70 to 85%). These findings lend considerable support to the concept that germinal centers in Peyer's patches are the site of generation of precursors of the IgA-secreting plasma cells that characterize mucosal immune responses, and also suggest that germinal centers may play an important role in the process of heavy chain class switching.
Alleles↗
Microanatomy of the thymus: its relationship to T cell differentiation.
The structure of the thymus can be determined by study at the light and electron microscopic levels, but relating it to the current knowledge of the thymus's function requires an approach that combines immunological and anatomical methods. The framework of the thymus consists of epithelial cells with interconnecting processes. Lymphocytes fill the spaces between the epithelial cells. In both the mouse and human thymus, immunological staining of tissue sections demonstrates that the principal cell bearing major histocompatibility complex (MHC) antigens is the epithelial cell. Differences are noted between I-A (HLA-DR) and H-2K/D (HLA-A, B) allotypic specificities in both species. Immunoelectron microscopy confirms the epithelial nature of these cells in both species. The continued expression of thymus-type MHC antigens in the thymuses of irradiated, bone marrow-reconstituted mice strongly suggests the synthesis of these antigens by the epithelial cells. Bone marrow-derived MHC antigens are largely confined to the medulla of the thymus.
Animals↗