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)

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which promotes fibroblast growth and collagen synthesis, but suppresses growth and differentiation of immune lymphocytes and killer cells. Immunohistochemical detection of TGF-beta 1 in Hodgkin's disease (HD) has been shown to correlate with the histologic feature of nodular sclerosis, which is associated with a favorable prognosis (American Journal of Pathology 1990, 136:1209). In that study, TGF-beta 1 was localized mainly at the margins of broad collagen bands (presumably sites of new collagen synthesis) and in areas containing numerous Hodgkin/Reed-Sternberg cells (H/RS). In these areas, TGF-beta 1 protein was found on the membrane and occasionally within the cytoplasm of H/RS cells. To determine whether TGF-beta 1 is synthesized by H/RS cells or secondarily bound to their membrane and sometimes internalized, we performed in situ hybridization (ISH) using 1.5 Kb 35S-labeled anti-sense and sense RNA probes to TGF-beta 1. Paraffin-embedded tissues of 10 cases from all histologic types of HD were examined. Somewhat unexpectedly, the major site of TGF-beta 1 mRNA was in eosinophils; TGF-beta 1 mRNA was not detected in H/RS cells. TGF-beta 1 mRNA was found in eosinophils in all cases of nodular sclerosis but not in other types of HD, despite the presence of numerous eosinophils in mixed cellularity cases. The presence of TGF-beta 1 mRNA coincided with immunohistochemical detection of TGF-beta 1 protein using antibody CC (1-30). These results confirm the role of TGF-beta 1 in the histogenesis of nodular sclerosing HD and indicate that eosinophils are the major source of TGF-beta 1 in this type of HD.
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PMID:Eosinophils are the major source of transforming growth factor-beta 1 in nodular sclerosing Hodgkin's disease. 842 49

Paraffin sections from 21 cases of Hodgkin's disease (HD), 18 cases of non-Hodgkin's lymphomas (NHL) and 15 cases of reactive lymphadenitides occurring in children 3-15 years old were examined by immunohistochemistry for the presence of c-myc and pan-ras oncogene products. In all cases of childhood lymphomas studied c-myc protein was expressed. The highest percentage was in HD where in 29% of cases the percentage of positive cells was greater than 20%, while in only 6% of NHL cases this percentage was noted. In all cases of reactive lymphadenitides the number of cells where c-myc was expressed was less than 5%. The ras oncogene was also found in HD but with a lesser degree of positivity than c-myc. In 48% of these cases the number of positive cells ranged between 2 and 10%, while in NHL and in reactive lymphadenitides there was no positivity. The above results indicate a frequent expression of c-myc protein in childhood lymphomas. This could reflect either an implication of c-myc oncogene in the pathogenesis of these tumor or an epiphenomenon of lymphomagenesis reflecting the proliferation rate of tumor cell population. Molecular biology studies are needed to clarify this issue.
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PMID:The expression of myc and ras oncogene protein in childhood lymphomas. 861 59

We have compared light chain immunohistochemistry in reactive lymphoid tissue and a series of paraffin-embedded B-cell lymphomas using standard trypsin digestion with a heat mediated epitope retrieval method. Fifty-seven B-cell lymphomas (18 high grade, 29 low grade and 10 cases of nodular lymphocyte predominance Hodgkin's disease), two reactive lymph nodes and eight tonsils fixed for known times between 12 h and 2 years were studied. Paraffin-embedded tissue was stained with polyclonal anti-kappa and anti-lambda antibodies. For each antibody staining was performed on two sections, one treated with trypsin digestion and one with microwave heating. Sections were scored from 0 to + + + with 0 representing poor staining and + + + excellent staining. A score of ++ was considered satisfactory. Light chain restriction was recorded if present. Satisfactory staining was obtained in 34/59 cases using trypsin digestion and 56/59 cases using heat retrieval. Light chain restriction was demonstrated in 32/57 (56%) B-cell lymphomas using trypsin digestion and 52/57 (91%) using heat retrieval. Satisfactory staining was obtained in tonsils fixed for up to 48 h using trypsin digestion and up to 2 years using heat retrieval. We have shown that for light chain immunostaining a heat mediated epitope retrieval method produces more consistent and satisfactory results and is effective over a greater range of fixation times than traditional trypsin digestion.
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PMID:Immunoglobulin light chain staining in paraffin-embedded tissue using a heat mediated epitope retrieval method. 897 59

Histologic features of recurrent Hodgkin's disease (HD) after conventional therapy are well known, but few studies describe HD after bone marrow transplantation (BMT). Histologic material from 63 patients who underwent BMT performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994 was examined; 13 of the 63 patients had histologically proved recurrent disease after BMT. Histologic material and clinical findings from the original diagnostic biopsy specimen and pre-BMT and post-BMT specimens were available from our study population of eight patients (five male, three female; age range, 16 to 38 years; median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of recurrence included lymph nodes only (four patients), and lymph nodes and lung, lung and liver, and lung only (one patient each). In one patient, a high-grade non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT. In another, disease progressed from grade 1 in the original biopsy specimen to grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT biopsy specimens of recurrent HD with lung involvement revealed a substantial increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase studies in seven patients demonstrated substantial change in phenotype of Reed-Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a +2 reaction with CD30 (Ki-1). No substantial differences in the reactive component were noted between the original biopsy specimen and pre-BMT and post-BMT specimens of recurrent disease. In summary, histologic findings of post-BMT recurrent NSHD do not differ significantly from those of the original diagnostic biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell lymphoma developed after BMT performed to treat recurrent HD.
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PMID:Recurrent Hodgkin's disease after bone marrow transplantation. 898 Mar 71

Recent studies in Western European populations have shown that peripheral T-cell non-Hodgkin's lymphomas (T-NHLs) are associated with Epstein-Barr virus (EBV) in a higher percentage than sporadic B-cell NHL (B-NHLs), and that the frequency of EBV-positivity might be influenced by the primary site of the tumor. Because of the geographic differences in EBV expression in Burkitt's lymphoma (BL) and Hodgkin's disease (HD), and the lack of studies of sporadic NHL from developing countries, we decided to survey the presence of EBV in a series of primary intestinal lymphomas from patients in Mexico and in Western Europe, and to analyze whether EBV status is influenced by tumor phenotype, and geographic or ethnic determinants. Paraffin-embedded tissue from 43 primary intestinal NHLs (19 cases from Mexico and 24 from Western Europe) were examined, including 17 high grade B-NHLs, 9 low grade B-NHLs, and 17 T-NHLs; 6 of which were enteropathy associated T-cell lymphomas. The distribution of histologic subtypes was similar in both groups. The presence of EBV was investigated with a combined approach using a nested polymerase chain reaction technique as well as immunohistochemistry for latent membrane protein-1 and in situ hybridization for EBV early RNA transcripts (EBER 1/2) RNAs. The median age of the Mexican patients was significantly lower than the median age of the European patients (32 v 62 years). This difference was most pronounced in patients with T-cell lymphoma (24 v 63 years). EBER-positive tumor cells were detected in 13 of the 43 (30%) cases of primary intestinal lymphoma, including 5 of 26 sporadic B-NHL (3 high grade and 2 low grade), and 8 of 17 T-NHL, all of which were classified as pleomorphic, medium and large cell. The rates of EBV-positivity were markedly different for European and Mexican cases. Whereas 7 of 7 (100%) T-NHL and 5 of 12 (42%) sporadic B-NHL of Mexican origin were EBER-positive, only 1 of 10 T-NHL and 0 of 14 sporadic B-NHL from Europe showed EBER expression in tumor cells. Latent membrane protein was positive in only 2 of 43 cases, 1 of which was an EBER-negative high grade B-NHL from Mexico that showed intact total mRNA in control hybridization. CD30 expression was found in 4 of 8 EBV-positive T-NHL and in none of the EBV-positive B-NHL. In contrast to European cases, intestinal NHLs from Mexico show a very high frequency of EBV-positivity, which is not limited to T-NHL, but includes a significant proportion of B-NHL. This study strongly suggests that similar to HD and probably BL, there are important epidemiologic differences in EBV association in intestinal T-cell NHL between European and Mexican populations. These differences might be the result of environmental factors, for example, earlier contact with childhood viruses on intestinal lymphomagenesis.
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PMID:Primary non-Hodgkin's lymphoma of the intestine: high prevalence of Epstein-Barr virus in Mexican lymphomas as compared with European cases. 900 68

Bax is a proapoptotic member of the Bcl-2 protein family. The incidence and prognostic significance of Bax protein expression in diffuse non-Hodgkin's lymphomas with a large cell component (DLCL) was determined by an immunohistochemical method by using paraffin-embedded tumors from a cohort of patients treated uniformly with combination chemotherapy (n = 139). All patients were between 16 and 70 years of age and had advanced stage disease of diffuse large cell type (diffuse mixed, diffuse large cell, immunoblastic, or anaplastic large cell). Paraffin sections from diagnostic biopsies were successfully immunostained for Bax in 113 cases. Of these, 7 (6%) tumors were scored as Bax immunonegative (< 1% Bax-stained tumor cells), 42 (37%) as low (1% to 10%), 9 (8%) as low-intermediate (11% to 30%), 25 (22%) as high-intermediate (31% to 70%), and 30 specimens (27%) as high for Bax expression (> 70%). Of the 7 Bax-immunonegative lymphomas, all also scored low (< or = 10% immunostained tumor cells) for Bcl-2 expression, whereas 78 of the 106 (74%) Bax-immunopositive tumors had low Bcl-2 expression. By itself, Bax expression was not of prognostic significance in univariate analysis, although there was a clear trend for patients with Bax-immunonegative lymphomas (n = 7) to relapse sooner and to die faster than patients whose tumors contained Bax-immunopositive malignant cells (n = 106; 8-year overall survival 29% versus 55%; P = .06). When combined with Bcl-2 immunostaining data, Bax provided additional prognostic information. Among patients with Bcl-2 low-expressing DLCLs, for example, Bax immunonegativity was associated with lower 8-year relapse-free survival (RFS; 29% v 61%; P < .01) and lower 8-year overall survival (OS; 29% v 63%; P < .05), suggesting that absence of Bax protein connotes a more aggressive phenotype when Bcl-2 protein is also not expressed at high levels. In contrast, low Bax expression was associated with improved 8-year disease-free survival (52% v 16%; P < .02), RFS (47% v 11%; P < .02), and OS (64% v 11%; P < .01) in patients whose tumors expressed Bcl-2 at high levels, suggesting that the combination of high levels of Bax and Bcl-2 expression is more deleterious than high levels of Bcl-2 expression alone. Bax expression failed to provide additional prognostic information beyond Bcl-2 expression in multivariate analysis that included the clinical International Prognostic Index factors (age, stage, lactate dehydrogenase, performance status, and number of extranodal sites) and immunophenotype. Taken together, the results suggest that Bax expression is not a major prognostic marker in DLCL. However, the interactions of the Bcl-2 and Bax expression data with respect to clinical outcome may shed new insights into the biological significance of Bcl-2/Bax protein heterodimerization.
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PMID:Prognostic significance of Bax protein expression in diffuse aggressive non-Hodgkin's lymphoma. 937

The products of the MTS1/CDKN2 and retinoblastoma (RB) tumor suppressor genes, p16 and pRB, act as agonists in controlling the late G1 cell cycle checkpoint. Inactivation of either gene occurs in a wide range of human malignant neoplasms. Data on the expression of both genes in the same set of malignant lymphoid neoplasms are scarce. We studied the p16/pRB pathway in low-grade and high-grade non-Hodgkin's lymphomas, using immunohistochemical techniques. Paraffin sections of 9 reactive lymph nodes and 43 low-grade and 60 high-grade malignant lymphomas were reacted with antibodies against pRB and p16. All benign lymph nodes showed a normal pattern of RB and MTS1/CDKN2 expression. Of 101 evaluable lymphomas, only a single high-grade tumor displayed loss of RB reactivity. Loss of p16 was identified in 14 of 55 evaluable high-grade lymphomas but not in any of the low-grade lesions. All but 3 of the RB- and p16-negative cases were diffuse large cell lymphomas, for an abnormality rate of 55% in this category. While loss of RB function was a rare event in human lymphomagenesis, p16 was absent in some 25% of high-grade non-Hodgkin's lymphomas; diffuse large cell lymphomas were the primary target of tumor suppressor gene inactivation.
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PMID:Loss of tumor suppressor gene expression in high-grade but not low-grade non-Hodgkin's lymphomas. 962 22

We investigated the prognostic value of proliferating cell nuclear antigen (PCNA) and p53 oncoprotein expression and of nucleolar organiser region (NOR) scoring, in relation to classic clinicopathological parameters, in a series of non-Hodgkin's lymphomas (NHL). Paraffin embedded tissue from 91 patients with NHL was stained immunohistochemically with the monoclonal antibodies PC-10 (PCNA) and DO-1 (p53) and histochemically with the AgNOR technique. The median follow-up was 48 (4 to 193) months. The impact of PCNA and p53 expression and of AgNOR number on survival was tested using univariate as well as multivariate analysis, in order to circumvent the heterogeneity in histologic grade, type and therapy. Univariate analysis identified seven variables related to overall survival: histologic type and grade, clinical stage, chemotherapy, p53 labelling index (LI), PCNA LI and AgNOR score, whereas only one parameter i.e. histologic grade influenced disease-free survival. In multivariate analysis stage, PCNA LI and AgNOR score predicted independently overall survival. PCNA was also the only independent predictor of post-relapse survival and histologic grade the most important indicator of disease-free survival. In conclusion, PCNA expression and AgNOR number may be better predictors of overall and post-relapse survival than histologic grade. The latter remains the most valuable prognostic indicator of disease-free survival.
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PMID:Prognostic implications of proliferating cell nuclear antigen (PCNA), AgNORs and P53 in non-Hodgkin's lymphomas. 971 25

To determine whether there might be immunophenotypic differences between nodular lymphocyte predominance Hodgkin's disease (NLPHD) and progressive transformation of germinal centers (PTGC) to aid in the differential diagnosis, we compared 16 cases of NLPHD with 13 cases of florid PTGC and 2 cases of focal PTGC. Paraffin-section immunohistochemistry was performed for CD20, CD45RA, CD45RO, CD3, CD43, CD57, EMA, CD30, and CD21. All PTGC cases showed well-circumscribed nodules of confluent sheets of CD20+ CD45RA+ small cells. T cells were scattered singly or in small groups. In 5 patients with florid PTGC, the T cells in some of the nodules formed rings around a few large transformed lymphocytes. In contrast, the nodules in all NLPHD cases showed an irregular, "broken-up" pattern with CD20 and CD45RA, and there were prominent T cell rosettes around the CD20+ large cells in all nodules. Rosettes of CD57+ cells and staining of large cells for EMA were seen in 3 and 2 cases of NLPHD, respectively, but not in PTGC. There were no differences between NLPHD and PTGC with respect to staining for CD30 or CD21. Three of the eight patients with florid PTGC and a few T cell rosettes had had persistent or recurrent lymphadenopathy; NLPHD developed in 1 of these patients 13 years later. We conclude that a combination of pan-B and pan-T antigens can be a useful adjunct to morphology in distinguishing NLPHD from PTGC. In approximately one-third of florid PTGC cases, T cell rosettes may be present, but they are notably fewer than those in NLPHD. Close follow-up of such patients may be appropriate.
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PMID:Progressive transformation of germinal centers and nodular lymphocyte predominance Hodgkin's disease: a comparative immunohistochemical study. 988 1

Previous results from B-cell chronic lymphocytic leukaemia suggest that expression of p27KIP1 might be important in protection from apoptosis. Given the relevance of apoptosis to the pathogenesis of Hodgkin's disease (HD), it was decided to examine the expression of p27KIP1 in relation to apoptosis in these lesions. Paraffin-wax sections from a total of 65 histologically confirmed HD tumours were used to derive apoptotic index (AI) and DNA fragmentation index (DFI) scores, which were compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), p21WAF1/CIP1 (p21) and cyclin D1, and with Epstein-Barr virus (EBV) status. The DFI was measured by TdT-mediated dUTP-FITC nick end-labelling (TUNEL), and the AI by conventional morphology. Cells showing the typical morphology of apoptosis, together with those resembling so-called 'mummified' Hodgkin/Reed-Sternberg (HRS) cells, were included in AI measurements. Increasing numbers of p27-positive HRS cells were associated with lower levels of apoptosis in these cells, as indicated by significantly lower AI and DFI scores. There was a trend towards poorer survival in those patients with the highest numbers of p27-positive HRS cells and with lower AI and DFI scores, but these differences were not statistically significant. p21-positive HRS cells were significantly more frequent in those cases with lower AI scores. A similar trend was observed for p21 and DFI, although this relationship was not statistically significant. There was also a trend towards higher levels of cyclin D1 protein in HD cases with high AI and DFI values. A tendency for increasing numbers of p27-positive and p21-positive HRS cells in EBV-positive cases was noted, but this relationship was not statistically significant. EBV status did not correlate with either AI or DFI scores. The results of this study suggest that p27, and possibly also p21, may be involved in protection from apoptosis in HD.
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PMID:Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1. 1072 87


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