Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type.
The high frequency of p53 mutation in NHL B cell lines and the relatively low frequency of p53 mutations in fresh lymphoma tissue suggests that p53 gene alteration may play a role in lymphomagenesis and/or disease progression in a subset of B cell lymphomas and that the p53 mutation conveys a proliferative advantage on lymphoma cells that permits their in vitro growth.
Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53.
Five of 6 BIBL samples with p53 mutations stained strongly for p53, but 20 lymphoma samples with no detectable p53 mutations also stained strongly for p53.
These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.
Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1 = 6 per cent (1/16); grade 2 = 48 per cent (10/21); grade 3 = 100 per cent (6/6).
Treatment outcome was correlated with the expression of p53 in the lymphoma, as measured by routine immunohistochemistry using the monoclonal antibody Do-7.
He was confirmed to have a germline mutation of the p53 gene by analysis of c-DNA from peripheral lymphocytes and loss of heterozygosity (LOH) of p53 was evident in the lymphoma.
Thus, there is a high frequency of p53 gene mutations in STS appearing in burn scars. p53 mutations were also frequent in pyothorax-associated lymphoma (PAL), a lymphoma that develops in patients with long-standing pyothorax, so p53 mutations might be frequent in malignancies that develop in chronic inflammatory sites.
To clarify whether a genetic predisposition for lymphoma is associated with constitutional p53 mutations, DNA from normal blood lymphocytes of 12 lymphoma patients with a family history of lymphoma and/or with metachronous lymphoma (median age 37 years) was examined for mutations of p53 exons 4-8.
To clarify the origin of the difference, we examined ionizing radiation (IR)-induced apoptosis in three closely related human lymphoma cell lines (DL-40, DL-95, and DL-110) that differ in p53 status.
Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients.
These data support a role of E2F-1 as tumour suppressor gene in lymphoma and strongly suggest that the RB1 and p53 pathways are important in the development of de novo DLCL.
Therefore, apoptosis is the only p53 function selected against during lymphoma development, whereas defective cell-cycle checkpoints and aneuploidy are mere byproducts of p53 loss.