The Epstein-Barr virus (EBV) genome has recently been identified in Hodgkin's disease (HD) and nodal non-Hodgkin's lymphomas (NHL). In order to elucidate the possible aetiopathogenetic role of EBV in benign and malignant lymphoproliferative disorders we investigated skin specimens from 24 patients with a primary cutaneous lymphoproliferative disorders (10 T-cell lymphomas 6 B-cell lymphomas and 8 pseudolymphomas) and from 22 normal individuals for the presence of EBV DNA using the polymerase chain reaction (PCR) technique and in situ hybridization (ISH) on formalin-fixed paraffin-embedded tissue sections. EBV DNA was identified by PCR in one of two cases of mycosis fungoides, in one of seven cases of pleomorphic T-cell lymphomas, in one case of centroblastic (CB) lymphoma of six B-cell lymphomas, and in three of eight pseudolymphomas. The EBV genome was also found in 2 of 22 specimens of normal skin. The small EBV-encoded nuclear RNAs, EBERs, were not detected in any PCR-positive sample by ISH. Based on our PCR and ISH findings, EBV does not seem to play a significant role in the development of cutaneous lymphomas.
Eight reactive lymphatic tissues, 166 cases of non-Hodgkin lymphomas (NHL) and 11 cases of multiple myeloma were investigated for expression of the c-abl protein using the poly-clonal anti-abl antibody 4411 and an indirect peroxidase technique. In selected cases the results were compared to those obtained with a second polyclonal and 2 monoclonal anti-abl antibodies. In 7 cases, Northern blot analysis of abl-mRNA was performed in parallel. In reactive lymphatic tissues, cells positive for the 4411 antibody were confined to the B-cell areas, i.e., to the mantle zone and parts of the germinal center. In NHL, a positive staining of the cell membrane was predominantly detectable in lymphomas putatively originating in the germinal center or mantle zone (in particular in centrocytic NHL), independent of their proliferative activity. Clinically, 7 out of 8 abl-positive cases of chronic lymphocytic leukemia (CLL) had a more aggressive course of disease, whereas "progressive disease" occurred in only 7 out of 19 c-abl antigen-negative cases. When the clinical status of 78 patients with NHL and 11 patients with multiple myeloma was related to c-abl expression, c-abl-positivity was mostly confined to patients in advanced tumor stages [p less than 0.001 (NHL)].
Epstein-Barr virus (EBV) is a gamma DNA herpes virus which is thought to play a part in the pathogenesis of some non-Hodgkin's lymphomas in individuals with or without immunodeficiency. We investigated 16 lymph nodal and 12 cutaneous anaplastic large cell lymphomas (ALCLs) (Ki-1+), all of which were in patients without immunodeficiency, for the presence of EBV genomes. The highly sensitive polymerase chain reaction (PCR) technique was employed for detection of viral DNA in extracts from formalin-fixed, paraffin-embedded tissue sections. In addition, we performed radioactive and non-radioactive in situ hybridization (ISH) for localization of EBV at the single cell level. EBV-DNA was demonstrated by PCR in five cases of nodal ALCLs (31%). All cutaneous ALCLs were negative. EBV-encoded small nuclear RNAs (EBERs) could be identified by ISH in the tumour cells of one of the five EBV-DNA-positive patients. Our results further support the concept that EBV may be involved in the development of a proportion of nodal ALCLs, but not in cutaneous ALCLs.
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