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.
It is suggested that mutations of the p53 gene and loss of normal p53 function are frequent in Hodgkin's disease and may be implicated in the pathogenesis of this disease.
To assess whether immunohistochemical positivity for p53 correlated with the presence of structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with high and low p53 values was amplified and sequenced to determine the existence of point mutations in the highly conserved regions of the p53 gene.
However, whether this "overexpression" of p53 protein reflects abnormality at the DNA level can no longer be assumed by immunocytochemistry alone. p53 from six Hodgkin disease-derived cell lines was examined by immunoprecipitation, polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis, and sequencing.
While a more detailed analysis of the p53 gene in HD is required, these data show that overexpression of p53 in HD is heterogeneous and that there is no simple correlation between EBV infection and p53 overexpression.
Based on these results, we conclude that the p53 mutated protein is present in a high number of cases with Hodgkin's disease, which is suggestive for an important event in the pathophysiology of the disease.
Our data suggest that the abnormal accumulation of MDM2 and p53 proteins in HD might reflect a derangement of molecular mechanisms that could play a pathogenetic role in this disease.
PCNA expression was high in neoplastic cells (> 50%) and variable (5-40%) in reactive lymphocytes in both HD and HD-like NHL. p53 positivity was found in RS cells and their variants in 64% of HD cases, but only in 25% of cases of HD-like NHL.
To address this question, 49 cases of HD have been investigated for p53 expression by immunohistochemistry, using the DO1 monoclonal antibody on paraffin sections.
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.
Twenty-one AIDS-related lymphomas, including five CD30-positive ALC and 11 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease (HD) specimens were characterized regarding the immunophenogenotypic features, the frequency and subtype distribution of EBV (as defined by in situ hybridization [ISH], Southern blot, and a polymerase chain reaction [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region) antigen expression (latent membrane protein-1 [LMP-1], EBNA-2, and for alterations of the tumor suppressor gene p53.
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 authors found p53 expression in RS-H cells in 16 of 30 cases of Hodgkin's disease (53%), with the percentage of RS-H positive cells ranging from 4% to 85%.
We conducted p53 mutational spectrum analysis in second lung cancers after radiation therapy for Hodgkin's disease in the Netherlands and in Ontario, Canada.
These results suggest that p53 mutation may represent an important mechanism in the pathogenesis of Hodgkin's disease, and this mechanism may be independent of Epstein-Barr virus.