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

The proliferative activity and the origin of multinucleated Reed-Sternberg cells and mononuclear variants in Hodgkin's disease have been studied in the past using several techniques. The presence of both proliferating-cell nuclear antigen and the cell-proliferation-associated antigen Ki-67 have also been reported in Hodgkin's disease. P34cdc2 is the protein product of the cell-cycle-control cdc-2 gene. Using a monoclonal antibody against the protein p34, cases of three different histological subtypes of Hodgkin's disease have been studied along with normal tonsil and follicular lymphoma as controls. In all these cases of Hodgkin's disease, positive p34 staining was seen in the majority of Reed-Sternberg cells and mononuclear variants (> 80%), along with a proportion of small lymphocytes, mainly T cells. Staining was predominantly cytoplasmic and occasionally additional nuclear signals were apparent. In two cases, double immunostaining with the anti-p34 antibody and CM-1 for p53 demonstrated positive signals for both proteins within the same neoplastic cells. Although the presence of p34 in Reed-Sternberg or variant cells reflects mitosis and hence suggests proliferation, the possibility of endomitosis remains and may explain the multinucleated appearance of Reed-Sternberg cells.
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PMID:Proliferation of Reed-Sternberg cells and variants in Hodgkin's disease. 817 8

We have investigated the p53 gene, expression of its mRNA, and stabilization of its protein in a series of non-Hodgkin's lymphomas (NHLs). Immunohistochemistry revealed positive staining of the p53 protein in node biopsies from 6/36 NHL patients, all of whom had high-grade disease. The remaining NHL samples, together with 3 reactive nodes, showed either negative staining or the staining of only occasional cells. In one case that exhibited intense nuclear staining in 90% of the cells, a mutation in the p53 gene was also observed. There was no evidence of rearrangements of the p53 gene in any of the NHL samples. Although p53 mRNA could not be detected in nonmalignant tissue, it was apparently overexpressed in 16/38 NHL, but this did not correlate with positive staining of the p53 protein. These data suggest that p53 dysfunction might play an important role in the evolution of some cases of NHL, and that mechanisms other than mutation of the p53 gene may be involved in stabilizing the p53 protein in these neoplasms.
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PMID:Analysis of the p53 gene, its expression and protein stabilization in non-Hodgkin's lymphomas. 817 25

In a search for specific serum markers with prognostic impact, we evaluated the clinical significance of IL-4, IL-7, and IL-8 as well as TNF receptor levels and soluble p53 in the serum of patients with untreated Hodgkin's lymphoma (HD). No elevations were observed for IL-4, while IL-7 and IL-8 were elevated in 15/52 (29%) and 21/78 (27%) patients, respectively. Soluble TNF receptors were detected in 16/29 patients (55%), and were significantly elevated in 6 (21%). P53 was detected in 21/33 (64%) patients. While IL-7 levels, detectable sTNF receptors, and p53 were not correlated with other obvious parameters, elevated IL-8 levels were associated with the presence of B symptoms (p < 0.002) and occurred more often in the nodular sclerosis form than in other histological subtypes (p < 0.02). Further investigations that correlate these serum parameters with the situation at the cellular level of an involved tissue will help to elucidate the enigmatic biology of HD.
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PMID:Interleukin-7, interleukin-8, soluble TNF receptor, and p53 protein levels are elevated in the serum of patients with Hodgkin's disease. 817 27

Expression of the p53 protein has been detected recently by immunohistochemistry in Hodgkin's disease (HD), but the relationship between p53 expression and the prognosis and clinicopathological heterogeneity of HD is still unclear. To address these questions we investigated 49 cases of HD for p53 expression by immunohistochemistry using the DO1 monoclonal antibody (MAb) on paraffin sections. Thirty-five cases were simultaneously tested with the 1801 MAb on frozen sections. Thirty-seven of 49 cases (75%) were DO1 positive while 14 of 35 (40%) were PAb 1801 positive. Both MAbs gave a nuclear staining restricted to Reed Sternberg cells (RSCs) and variants and distributed among the three HD subtypes analyzed (ie, nodular lymphocyte predominant, nodular sclerosing, and mixed cellularity). The percentage of positive neoplastic cells in each case was heterogeneous, ranging from almost 100% to less than 5%. In 39 patients for whom clinical data were available statistical analysis did not show any significant correlation between p53-positive immunostaining and clinical staging, B symptoms, probability of relapse, or disease-free survival. We conclude that p53 expression is a common event in HD regardless of histological subtyping, but does not bear any pejorative significance.
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PMID:Expression of the p53 gene in Hodgkin's disease: dissociation between immunohistochemistry and clinicopathological data. 820 Jun 35

The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non-Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance.
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PMID:Biologic and molecular characterization of non-Hodgkin's lymphoma. 821 89

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas represent a significant and formidable clinical problem. They also represent an important biologic model for investigating the development and progression of high-grade malignant lymphomas and for studying lymphomas that develop in the setting of immune deficiency. A vast majority of non-Hodgkin's lymphomas exhibit clonal immunoglobulin gene rearrangements and, hence, are B-cell neoplasms. Most express B-cell phenotypes, but a minority, predominantly body cavity-based tumors, express indeterminate phenotypes. AIDS-associated non-Hodgkin's lymphomas do not contain HIV. However, approximately 40% of systemic non-Hodgkin's lymphomas, predominantly those with immunoblastic plasmacytoid morphology, and essentially 100% of primary central nervous system AIDS-associated non-Hodgkin's lymphomas contain Epstein-Barr virus. The c-myc protooncogene is rearranged in approximately 80% of systemic cases, predominantly in those with Burkitt's and Burkitt's-like morphology. Point mutations of the ras gene are detectable in approximately 15% of systemic cases. The p53 tumor-suppressor gene is mutated in approximately two thirds of systemic AIDS-associated Burkitt's and Burkitt's-like non-Hodgkin's lymphomas. The retinoblastoma tumor-suppressor gene does not appear to be mutated or deleted in AIDS-associated non-Hodgkin's lymphomas. In summary, various genetic lesions occur in AIDS-associated non-Hodgkin's lymphomas, which appear to vary according to the anatomic site of disease (systemic vs central nervous system vs body cavity) and the histopathology (Burkitt's vs immunoblastic vs large cell). Further active investigation is necessary to determine the role of these and possibly other genetic lesions in AIDS lymphomagenesis.
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PMID:Biologic aspects of AIDS-associated non-Hodgkin's lymphoma. 821 97

In this paper a multimarker immunohistochemical technique is described in detail which allows the quantitative evaluation in situ of cells expressing abnormal accumulation of p53 phosphoprotein together with the CD30 antigen, a well known marker of Hodgkin's and Reed-Sternberg cells. The method is useful to define quantitatively the proportion of phenotypically abnormal cells in the complex microenvironment of Hodgkin's lesions, and to compare the phenotypical derangement of p53 gene with molecular biology data obtained on the same samples.
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PMID:Quantitative approach to the immunohistochemical analysis of p53 antioncogene and CD30 antigen in Hodgkin' disease. 821 85

p53 overexpression has been found to be a fairly common feature in high grade lymphomas in the majority of tumoral cells. The results vary from series to series, from 25% to 33% of cases. To assess whether immunohistochemical positivity for p53 correlated with the presence of structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with high and low p53 values was amplified and sequenced to determine the existence of point mutations in the highly conserved regions of the p53 gene. In the group of 8 cases containing high levels of protein, 3 cases showed missense point mutations at the codons mapping between exons 5 through 8. Of the 8 cases of tumors containing undetectable or low levels of p53 protein, 1 case presented a nonsense point mutation giving a stop codon. No missense mutations were detected in this group. The finding of p53 mutations in 4 of 16 cases confirms the presence of p53 gene mutations in high grade lymphomas distributed over different histologic groups. These include Burkitt's lymphoma, together with centroblastic, immunoblastic, and large cell lymphoma of mucosa origin. Nevertheless, the absence of mutations in 5 of the 8 cases that overexpressed p53 suggests that the nuclear or cytoplasmic stabilization of p53 protein could also depend on other factors. The absence of detectable levels of p53 protein cannot discount the existence of p53 mutations, as is shown by a case of Burkitt's lymphoma in which a nonsense mutation was detected. The impact of this range of p53 alterations on clinical course and treatment response of the patients deserves to be explored, in an attempt to differentiate the specific consequences of each one.
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PMID:The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations. 821 4

p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.
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PMID:Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood. 821 5

P53 is an oncosuppressor gene which is located on chromosome 17. Mutations of the p53 gene are closely associated with malignant transformation under in vitro conditions and are the most common genetic alteration in human malignancy. Unlike normal p53 protein which is unstable and usually cannot be detected by immunohistology, mutated p53 shows a decreased cell turnover rate and overexpression as compared with the wild-type protein. In this study a panel of four anti-p53 antibodies (PAb240, PAb421, PAb1801 and DO7) was applied to 52 cases of Hodgkin's disease: three cases of nodular lymphocytic predominance (LP), 33 cases of nodular sclerosis (NS), and 16 cases of mixed cellularity (MC). The results show that 53 protein is present in the Hodgkin's- and Reed-Sternberg cells in 82% of NS and 94% of MC, but not in nodular LP. It is suggested that mutations of the p53 gene and loss of normal p53 function are frequent in Hodgkin's disease and may be implicated in the pathogenesis of this disease.
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PMID:P53 protein expression in Hodgkin's disease. 824 Jul 88


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