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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.
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PMID:De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct. 754 11

The transmembrane glycoprotein CD44 exists in a variety of isoforms generated by alternative splicing of the pre-mRNA. In a rat metastasis model, certain variant isoforms (containing exon 6v) are causally involved in lung metastasis formation. We have summarized the data obtained to date on the expression of CD44 variant isoforms in human tumour progression. In non-Hodgkin lymphomas, expression of exon 6v containing isoforms is an independent prognostic factor indicating an adverse prognosis. Upregulation of exon 9v containing isoforms in gastric and renal cell carcinomas relates to a poor prognosis of patients. In colorectal carcinomas, CD44-9v isoforms are strongly expressed already in early adenomas; CD44-6v isoforms are upregulated in late adenomas along with ras and TP53 mutations. No expression of variant isoforms has been detectable in neuroblastomas, but significant downregulation of CD44s correlates inversely with tumour progression and N-myc amplification. Only in breast carcinoma has no correlation of CD44 expression with survival or any other prognostic marker been established. Evaluation of CD44 isoform expression by immunohistochemistry in cases of non-Hodgkin lymphoma, gastric, colon and renal cell carcinomas, as well as neuroblastomas, may be a useful diagnostic parameter indicating invasive processes.
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PMID:Are CD44 variant isoforms involved in human tumour progression? 755 60

Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.
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PMID:Molecular analysis of cutaneous B- and T-cell lymphomas. 757 11

Mutation and abnormal expression of p53 was studied in 38 lymphomas [five Hodgkin's disease and 33 non-Hodgkin's lymphoma (NHL)]. CM1 polyclonal antibody was used to detect overexpression of p53. Three missense mutations were characterised in three cases of NHL after screening exons 5-8 of p53 of all the tumours with single-strand conformation polymorphism (SSCP) analysis. Only two out of three tumours with a missense mutation showed abnormal expression of p53 as measured by CM1. Conversely, seven out of nine tumours with positive CM1 staining had no point mutation demonstrated. Overexpression of p53 in the cases of NHL occurred in three out of twenty four low-grade tumours and five out of nine high-grade tumours (Kiel classification). The results suggest that abnormalities of p53 are commoner in high-grade than low-grade NHL, and that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53.
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PMID:p53 mutation and expression in lymphoma. 759 45

Expression of the p53 protein can be detected by immunohistochemistry in Reed-Sternberg (RS) cells, the presumed neoplastic component of Hodgkin's disease (HD) lesions. At present, there is no clear molecular evidence that p53 positive immunostaining in HD correlates with the presence of mutations or other structural alterations of the p53 gene. To address this question, 49 cases of HD have been investigated for p53 expression by immunohistochemistry, using the DO1 monoclonal antibody on paraffin sections. Thirty-seven out of 49 cases (75 per cent) exhibited positive immunostaining restricted to RS cells and variants. Among these 37 positive cases, ten cases were selected on the basis of a rich content of RS cells showing virtually 100 per cent DO1 positivity. A PCR-mismatch strategy was chosen for the detection of p53 mutations. The threshold level of sensitivity was assessed on positive cell-line controls. A proportion of 10-15 per cent p53 mutated cells mixed in a normal population could be identified. Total genomic DNA was extracted from the ten selected HD cases and PCR amplification of exons 5-8 of the p53 gene was performed. Heteroduplex mismatch analysis revealed no structural alterations of the p53 gene in any case. In view of these findings, it appears unlikely that the sensitivity of the method by itself can fully explain the negative results, although this possibility cannot be completely ruled out. Thus, it is conceivable that p53 positive immunostaining in HD may not necessarily imply genomic alterations in the classic 'hot spot' regions and may be related to another mechanism of p53 protein stabilization.
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PMID:PCR-mismatch analysis of p53 gene mutation in Hodgkin's disease. 773 14

In patients infected with HIV, high-grade B-cell non-Hodgkin's lymphomas (NHL), including the small noncleaved cell (SNCC) category, exhibit pleomorphic features, which makes precise definition difficult. Sixty-nine pathologic specimens with HIV-related systemic lymphomas, including 42 SNCC, 20 immunoblastic lymphomas (IBL), and 7 cases with features "intermediate" between SNCC and IBL were morphologically and immunophenotypically investigated. The host immune status was also analyzed in 57 of 69 patients. In 29 representative SNCC lymphomas, in 9 IBL cases, and an additional 3 intermediate lymphomas, both p53 protein overexpression and the association of Epstein-Barr virus (EBV) genetic information were assessed. Small noncleaved cell lymphomas included tumors exhibiting features of the 2 established subtypes (27 Burkitt's and 15 non-Burkitt's). In the seven intermediate cases, cells showed features intermediate between SNCC with plasmablastic differentiation and immunoblasts plasmacytoid. Immunoblast-like cells were also present. p53 protein overexpression and EBV association were found in a proportion of SNCC (14 of 29; 7 of 29) and intermediate (3 of 3; 2 of 3) lymphomas. Conversely, IBL cases were consistently p53 negative, but showed a high EBV association (7 of 9). All the evaluated patients with intermediate lymphomas had a considerably lower mean (76.6 per mm3 +/- 77.4 SD) and median (54 per mm3) number of CD4+ lymphocyte count than SNCC patients (mean 227.9 per mm3 +/- 186.9 SD, median 193 per mm3), thus mirroring IBL patients (mean 95.3 per mm3 +/- 82.8 SD, median 81 per mm3). All data provide evidence that lymphomas showing intermediate features constitute a distinct subgroup from either SNCC or IBL.
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PMID:AIDS-related Burkitt's lymphoma. Morphologic and immunophenotypic study of biopsy specimens. 774 Nov

p53 protein overexpression is a frequent finding in non-Hodgkin's lymphomas (NHL), being detected in over 25% of the cases. Moreover, some high-grade lymphomas and a large fraction of low-grade tumors show a pattern of scattered p53 accumulation in a limited percentage of neoplastic cells. In contrast, NHLs show a low frequency of p53 gene mutations. To investigate the molecular bases of p53 protein overexpression, a large series of NHLs was analyzed for p53 gene status. The analysis of the entire coding region of the gene (exons 2-11) and corresponding donor and acceptor splicing sites indicated that a significant proportion of p53-positive tumors overexpresses a wild-type form of p53 protein (wt-p53). To assess whether wt-p53 accumulation was related to the formation of inactive complexes with endogenous proteins, MDM2 oncogene expression and amplification were analyzed. MDM2 overexpression was detected only in one third of the wt-p53-positive cases, thus excluding that MDM2 accounts tout court for the accumulation of a normal p53 protein. However, the fact that MDM2 overexpression was detected in only the p53-positive cases and the observation that MDM2-positive cells were a subpopulation of p53-positive cells suggest a link between the two phenomena. In particular, our results indicate that the accumulation of a wt form of p53 protein could promote the overexpression of the MDM2 gene product. In addition, the prevalence of MDM2 positivity in intermediate/high-grade tumors together with the concordant expression of wt-p53 and MDM2 only in the high-grade component of a 'composite' lymphoma suggests that perturbation in the MDM2/p53 critical ratio could play a role in lymphoma progression.
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PMID:MDM2 overexpression does not account for stabilization of wild-type p53 protein in non-Hodgkin's lymphomas. 775 55

HHV-6 infected immature T (HSB2) and Hodgkin (HDLM2) cells and biopsy tissues from lymph nodes of patients with Hodgkin's disease (HD) and Kikuchi lymphadenitis (KL) were studied immunohistologically for virus antigen expression and for the oncogene/anti-oncogene products ras, bcl-2 and p53. Cell proliferation and cell death were tentatively monitored in tissue culture by PCNA staining, by viability testing and in situ end labeling of fragmented DNA. PCNA was also used in biopsy samples. KL is characterized by high incidences of focal cell death (i.e. histiocytic necrotizing lymphadenitis), while HD is apparently more a proliferative disease. The techniques used revealed no significant differences in the cellular expression of viral DNA or antigens among cell lines, HD or KL. The HDLM2 cell line with the superior survival after HHV-6 infection showed a significantly lower expression of p53 and PCNA than HSB2 cells. Biopsy samples from patients with KL did not express p53, and ras and PCNA were observed in fewer cells than in HD. Bcl-2, however, was significantly more frequently seen than in HD. The interpretation of the data is difficult; they suggest that there are additional regulatory influences in control of cell proliferation and cell death, such as cytokines and growth factors, which are altered after viral infection. Also, virus-induced cell death probably includes other mechanisms besides apoptosis, such as cell damage caused by oxygen radicals.
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PMID:[Apoptosis and cell proliferation in HHV-6 infections. Regulatory mechanisms of p53/bcl-2/ras interactions]. 776 57

The neoplastic nature of Hodgkin's disease (HD) is suggested by several lines of evidence, including aggressive clinical course, presence of proliferating atypical cells morphologically recognized as Hodgkin's and Reed-Sternberg cells (H-RS), aneuploidy, and, in the minority of cases, clonality. Nevertheless, the etiopathogenesis of HD still remains elusive, and probably diverse. This uncertainty is partly due to the peculiar histology of HD lesions, characterised by the paucity of the putative neoplastic cell component, i.e. H-RS cells, admixed to a variety of reactive cells which prevent an exhaustive investigation at molecular level. Nevertheless, the possible involvement of different molecules with oncogenic potential has been recently suggested on the basis of immunohistological and molecular biology studies. These include oncogenes such as bcl-2 and MDM2 and anti-oncogenes such as p53. In addition, a large amount of data has accumulated on the possible role of EBV infection in HD. The colonization of lymphoid tissues by immortalized H-RS cells can account for the derangement of cytokine networks leading to microenvironmental and systemic abnormalities. In addition, a variety of soluble receptors (sIL-2R, sCD30, sTNF-R), and adhesion molecules (sICAM-1) are abnormally produced at sites of disease involvement. Some of these molecules still retain the ability to bind their ligands and can potentially contribute to the derangement of immune mechanisms observed in HD. Many of these soluble molecules can also be found in the patient's sera providing new potential prognostic and follow-up parameters in HD patients. The comparative analysis of the same molecules within the tissue, using immunohistochemistry, and in the blood, using immunochemical assays, appears as a promising informative approach.
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PMID:Biopathologic features of Hodgkin's disease. 778 48

This review addresses several current questions about Hodgkin's disease (HD): 1) Does HD represent a single disease or multiple diseases? 2) What is the role of cytokines in HD? 3) What is the nature of the Reed-Sternberg cell? 4) How are Epstein-Barr virus (EBV) and oncogenes (bcl-2, c-myc, and p53) involved in the pathogenesis of HD? Nodular lymphocyte predominance HD appears to be a distinct clinicopathologic entity. Cytokines attract inflammatory cells, induce fibrosis, upregulate oncogenes and adhesion molecules, cause systemic symptoms, and mediate immune suppression. Reed-Sternberg cells are derived from B and T lymphocytes in most instances, although an alternative origin from a follicular dendritic reticulum cell has been proposed. EBV is an etiologic agent in some but not all HD cases. EBV gene products confer a growth advantage on Reed-Sternberg cells. The bcl-2 and p53 oncogenes protect Reed-Sternberg cells from apoptosis and are not directly upregulated by EBV.
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PMID:Pathology of Hodgkin's disease. 782 47


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