Showing papers by "Andrew J. Norton published in 1993"

Epstein–barr virus in hodgkin disease relation to age and subtype

Abstract: Background Epstein-Barr virus (EBV) has been associated with Hodgkin disease (HD), but its relationship to the age of the patients and the histologic subtype is not well defined The possibility that other lymphotropic herpesviruses, such as cytomegalovirus (CMV) and human herpesvirus type 6 (HHV-6) could be involved in the pathogenesis of HD is also unclear Methods Paraffin-embedded material from 77 cases of HD was studied This consisted of 24 specimens from children (mean age, 114 years), 36 from young adults (mean age, 288 years), and 17 from older adults (mean age, 538 years) EBV was detected in Hodgkin and Reed-Sternberg cells (HR-S) by a sensitive in situ hybridization technique based on the detection of Epstein-Barrencoded RNA Viral activity was subsequently demonstrated in HR-S cells by using monoclonal antibodies to EBV latent membrane protein Results EBV was found in a total of 25 of 77 cases (32%) There was no significant difference in EBV positivity between the different age groups However, the prevalence of EBV varied between different subtypes: 68% of mixed cellularity cases were found to be positive by contrast with 24% nodular sclerosis, 0% lymphocyte predominant, and 14% lymphocyte depleted Analysis of the histologic reports of a further 783 cases of HD to determine the age distribution of the different subtypes revealed an absence of an older adult second peak in the age distribution curve In situ hybridization for CMV and HHV-6 was negative in all cases Conclusions It was concluded that EBV is predominantly associated with mixed cellularity HD, and there is no correlation with the age of the patient

Epstein-Barr virus in angioimmunoblastic T-cell lymphomas.

Abstract: Epstein-Barr virus (EBV) has been proposed as a possible infective agent involved in the pathogenesis of angioimmunoblastic lymphadenopathy (AIL), a progressive and often fatal lymphoproliferative disorder. We have studied 19 cases of AIL-like lymphomas for the presence of EBV using a sensitive in situ hybridization technique based on the detection of Epstein-Barr encoded RNAs with digoxigenin-labelled oligonucleotide probes. EBV was found in 11 cases; in seven of these EBV was detected in occasional cells. Immunocytochemical studies to investigate viral gene expression, revealed the presence of EBV-encoded latent membrane protein only in those cases which had appreciable numbers of positive cells by in situ hybridization. The intensity of staining varied from case to case and the overall proportion of cells staining for latent membrane protein in a given case was considerably less than that by in situ hybridization. In situ hybridization for cytomegalovirus and human herpes virus type-6 was negative in all cases. We discuss these findings in the light of the proposed role of EBV in the pathogenesis of AIL and conclude that the presence of EBV is a consequence of the disease rather than the cause.

Epstein–Barr virus in Reed–Sternberg G‐like cells in non Hodgkin's lymphomas

Abstract: In the course of our study on Hodgkin's disease (HD), ten cases of non-Hodgkin's lymphomas (NHL) containing Hodgkin and Reed-Sternberg-like (HRS) cells were encountered. Many of these cases had initially been diagnosed as HD, but on careful review of the histology, with the aid of immunophenotyping studies, they were reclassified as NHL. The presence of Epstein-Barr virus (EBV) in these HRS-like cells was investigated using a combination of EBER in situ hybridization (ISH) and immunostaining for the detection of EBV-encoded latent membrane protein (LMP). HRS-like cells in four cases (two lymphoplasmacytoid lymphomas, one Richter's transformation of lymphoplasmacytoid lymphoma, and one immunoblastic lymphoma of T-cell type) were found to be EBV-positive. In two of these cases, a second biopsy taken up to 10 years later also contained EBV in the HRS-like cells. In three of the four cases, HRS-like cells expressed the activation antigen CD30, but the expression of B- or T-cell antigens was variable. All cases of T-cell-rich B-cell lymphomas were negative for EBV. In conclusion, EBV may play a role in the development of HRS-like cells in some cases of NHL. The relationship of HRS-like cells to HRS cells of HD is discussed.

p53 protein expression in Reed-Sternberg cells of Hodgkin's disease.

Abstract: Hodgkin's disease (HD) is perceived to be a malignant disease of the lymphoid system. One of the main obstacles into the investigation of the cell biology of Hodgkin's disease is the relative paucity of Reed-Sternberg cells (or variants), the presumed neoplastic component of this condition, which often make up less than 1o of the total cell number. The p53 gene, located on the short arm of chromosome 17, has been described as a tumour suppressor gene producing a 53kD nuclear DNA-binding phosphoprotein (1). Several lines of evidence support the notion that the loss of or alteration in p53 may contribute to the deregulated growth characteristic of cancer cells (2). Overexpression of p53 has been shown in numerous human malignant tumours using monoclonal antibodies