Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor proliferative activity, or labeling index, is of interest for gaining insight into the biologic properties of human neoplasm and for providing clinical information that might guide patient management. There has been an abundance of literature reporting experience with standard and newer techniques of measuring tumor proliferative activity. These methods are reviewed with emphasis on technical issues. Particular attention is paid to the development and use of monoclonal antibodies, Ki-67 and anti-PCNA/cyclin. These antibodies are readily available and relatively simple to use. The former has recently been shown to be of prognostic value in non-Hodgkin's large cell lymphomas. A number of studies suggest that indices using these techniques could be useful for a variety of carcinomas, soft tissue tumors, and tumors of the central nervous system.
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PMID:Measures of tumor proliferative activity. 136 73

Measurement of growth fraction is an important way to provide an objective assessment of non-Hodgkin's lymphomas; however, many of the techniques used require fresh tissue and/or special instrumentation. Recently, antibodies to the proliferating cell nuclear antigen (PCNA)/cyclin reactive in paraffin-embedded sections have become available. To investigate the utility of one such antibody in the study of follicular center cell (FCC) lymphomas and cleaved cell lymphomas of centrocytic type (CC), paraffin sections from 40 cases that had been characterized in two previous morphometric studies were stained with a PCNA antibody. Strong correlations were found between PCNA staining in formalin- and B5-fixed tissues, between the overall proportion of PCNA-positive cells and the proportion in the area of greatest staining, and between strong and total staining. Proliferating cell nuclear antigen staining was significantly stronger in the noncleaved FCC lymphomas than in the cleaved cell lymphomas. The FCC lymphomas showed moderate to strong correlations between PCNA staining and morphometric features of transformation, but only nuclear area correlated with PCNA staining in the CC group. Proliferating cell nuclear antigen staining was not significantly different between CC lymphomas with and without the characteristic bcl-1/PRAD 1 gene rearrangement. In summary, PCNA staining of either B5- or formalin-fixed, paraffin-embedded tissue sections is a simple aid in the objective categorization of FCC lymphomas and may offer additional potentially prognostic information in some FCC subsets and in CC lymphomas. The findings further support the distinction between CC and true FCC lymphomas.
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PMID:Growth fraction in centrocytic and follicular center cell lymphomas: assessment in paraffin sections with a proliferating cell nuclear antigen antibody and morphometric correlates. 768 24

Proliferating cell nuclear antigen (PCNA/cyclin) is a useful marker of proliferation and its expression correlates with prognosis in some human neoplasms. The clinical course of nodular sclerosis Hodgkin's disease (NSHD) varies in both grades (NSI, NSII) as defined by the British National Lymphoma Investigation. Expression of PCNA in Reed-Sternberg cells and their variants was evaluated in NSI and NSII. There were no significant differences in the ratio of PCNA-positive cells in both groups. The results suggest that differences in the clinical course do not depend on the proliferative rate of Reed-Sternberg cells and their variants in NSHD.
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PMID:Percentage of proliferating cell nuclear antigen (PCNA)-positive Reed-Sternberg cells in nodular sclerosis Hodgkin's disease. 790 58

BCL1/PRAD1 gene rearrangements involving the cyclin D1 gene are a feature of about 70% of centrocytic/mantle-cell lymphomas (CC/MCL) but are identified in only a small proportion of other B-cell non-Hodgkin's lymphomas. Of 37 lymphomas found to have BCL1/cyclin D1 (PRAD1, CCND1) gene rearrangements, 30 fit the morphologic and immunophenotypic criteria for typical CC/MCL. Seven cases with morphologic features atypical for CC/MCL were identified. CD5+ monoclonal B cells were documented in all these cases. Six cases were subsequently stained for cyclin D1 protein, and all showed nuclear positivity. Five cases had variably sized foci of cells with moderately abundant pale cytoplasm resembling parafollicular/monocytoid B cells, marginal zone cells, hairy cells, or even proliferation centers. Transformed-appearing cells were also present in some lymphomas. In one case, striking follicular colonization created a markedly nodular growth pattern mimicking a follicular lymphoma. A sixth case had a marked predominance of small, round lymphocytes at some sites, mimicking a small lymphocytic lymphoma. Five of these six cases also had areas more typical of CC/MCL. The seventh case was a CD5-positive splenic marginal zone-like lymphoma (SMZL) with plasmacytic differentiation and circulating villous lymphocytes consistent with a splenic lymphoma with villous lymphocytes (SLVL). These cases illustrate the morphologic spectrum of small B-cell lymphoid neoplasms that have BCL1/cyclin D1 gene rearrangements and overexpression of cyclin D1. Despite the BCL1 translocation and cyclin D1 overexpression, the splenic lymphoma with plasmacytic differentiation was definitely not a CC/MCL and fit the clinicopathologic entity of SMZL/SLVL. The other six cases are best considered CC/MCL variants based on a combined morphologic, immunophenotypic, and genotypic evaluation. Genotypic or immunophenotypic studies to identify cyclin D1 rearrangements and overexpression, although not pathognomonic, are useful in recognizing these variant CC/MCL cases, which can mimic almost any of the other well-described but more indolent low-grade B-cell lymphomas and leukemias. Some of the variant CC/MCL cases had features in common with the CD5+ cyclin D1+ SMZL/SLVL, suggesting a possible relationship between these two otherwise distinct entities.
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PMID:The morphologic spectrum of non-Hodgkin's lymphomas with BCL1/cyclin D1 gene rearrangements. 861 27

Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrangement and constant cyclin D1 (PRAD-1/CCND1) gene overexpression. Cyclin D1 is a G1 cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb). Inactivation of the Rb tumor suppressor gene has been implicated in the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin D1, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot. Rb gene structure was studied in 13 cases by Southern blot. Cytogenetic analysis was performed in 5 cases. The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73). Blastic variants showed higher numbers of pRb-positive cells (mean, 29%) than the typical cases (10%; P < 0.005) by immunohistochemistry and, concordantly, higher levels of expression by Western blot. In addition, the blastic cases also had an increased expression of the phosphorylated protein. No alterations in Rb gene structure were observed by Southern blot analysis. Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors. These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors. Cyclin D1 overexpression may play a role in the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.
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PMID:Expression of retinoblastoma gene product (pRb) in mantle cell lymphomas. Correlation with cyclin D1 (PRAD1/CCND1) mRNA levels and proliferative activity. 862 27

p21 is induced by and mediates the effects of p53 in response to DNA damage arresting the cell in G1 or G2, by inhibiting multiple cyclin-cyclin-dependent kinases (CDK) or binding to proliferating-cell nuclear antigen (PCNA), respectively. To determine whether p21 mutants occur in tumors we examined DNA from 188 primary non-Hodgkin's B-cell lymphoma (NHL) tumors and 84 chronic myelogenous leukemia samples for mutational changes in the coding region of p21 by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA. We did not find mutations in the coding region in these two tumor types. We identified a polymorphic nucleotide change in codon 31 in which a transversion from C to A substituted amino acid arginine for serine. Three of 188 NHL tumors were homozygous for this change, but they were not identified in 84 CMLs or in 97 normal controls. On the other hand, in one CML case a transition from G to A in codon 64 substituted amino acid threonine for alanine. These data do not indicate that derangements in the coding region of p21 contribute to the initiation and/or progression of these tumors.
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PMID:Absence of somatic changes in p21 gene in non-Hodgkin's lymphoma and chronic myelogenous leukemia. 865 61

p21WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs;253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single-strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30-NHL and in only 8 of 36 (22.2%) CD30+cases, which were mostly anaplastic large-cell lymphomas. A consistent number (> 10%) of p21WAF1-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+cases (25/36 [69.4%]), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30-group, neoplastic cells were p53+/p21-. In all of these cases, the p53+cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.
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PMID:p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function. 891 68

Mutations in the p53 tumour suppressor gene are the most common genetic alteration found in human cancers. Most of them are accompanied by stabilization of the protein, which renders it detectable through immunohistochemical techniques. Although p53 expression is a very common finding in Hodgkin's disease (HD), the status of the p53 gene is scarcely known, due to the difficulty in sequencing this gene in a lesion in which tumour cells are thought to constitute a very minor subpopulation, diluted in a background of supposedly benign cells. The pattern of expression of two downstream p53 proteins (MDM2 and p21 WAF1/CIP1, was studied as an indirect way of assessing p53 gene status. MDM2 is a wild-p53 inducible protein which may form a complex with p53, abrogating its function, as has been found in human sarcomas and other malignancies. p21WAF1/CIP1 is another protein inducible by wild-type p53, involved in inhibiting cell-cycle progression, through binding to cyclin/cyclin-dependent-kinase complexes. MDM2 and p21WAF1/CIP1 immunostaining was detected in all the cases analysed, independently of histological type, and were mainly present in Sternberg-Reed and Hodgkin (H & SR) cells. These immunohistochemical results were confirmed by Western blotting. To study the cause of MDM2 protein accumulation, MDM2 mRNA expression was also investigated by reverse transcription polymerase chain reaction (RT-PCR). The results show the presence of MDM2 transcripts in all cases of HD, albeit at lower levels than those found in reactive lymphoid tissue. These results seem to support the hypothesis that p53 is transcriptionally active in at least some of the H & SR cells in HD, and is able to induce MDM2 and p21WAF1/CIP1 protein expression.
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PMID:MDM2 and p21WAF1/CIP1, wild-type p53-induced proteins, are regularly expressed by Sternberg-Reed cells in Hodgkin's disease. 894 16

Mantle-cell lymphoma comprises 2%-10% of all non-Hodgkin's lymphomas (NHLs). Patients present with generalized disease, and have a poor prognosis. Three different histologic patterns (mantle zone, nodular, and diffuse) and three different cytological variants (classical, blastic, and pleomorphic) have been described. The phenotype (strong surface IgM, CD5+, CD10-, CD23-, cyclin D1+ and B-cell markers+) is remarkably constant. Dependent on the methods used (PCR, Southern blot analysis, and cytogenetics) a t(11;14) can be detected in approximately 35%-66% of cases. Using FISH analysis, possibly almost all cyclin D1-expressing MCLs carry this translocation, indicating that a substantial part of these translocations are missed by conventional methods. This has been confirmed by DNA fiber FISH analysis by which the breakpoints could be accurately mapped over a 220 kb region centromeric of the cyclin D1 gene. Additional genetic abnormalities involve breakpoints and deletion at the 3' end of the cyclin D1 gene, numerical chromosomal aberrations, mutations in p53, and deletions of p16. These may be associated with tumor progression. Owing to the translocation t(11;14), the cyclin D1 gene is activated. At the RNA level, approximately 90% of MCLs show overexpression. This corroborates immunohistochemistry on paraffin tissue sections. Since expression of cyclin D1 in normal lymphoid cells is very low to undetectable, and only hairy-cell leukemia and very few other B-cell lymphomas show expression, immunohistochemistry for cyclin D1 provides an excellent marker for MCL. In hairy-cell leukemia, expression is moderate and cannot be explained by chromosomal translocation.
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PMID:Bcl-1/cyclin D1 in malignant lymphoma. 920 53

cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.
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PMID:cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas. 956 96


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