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P53 and P21 Proteins Combined with the International Prognostic Index Can Improve the Prediction of Outcome in Patients with Diffuse Large B-Cell Lymphoma


, : P53 and P21 Proteins Combined with the International Prognostic Index Can Improve the Prediction of Outcome in Patients with Diffuse Large B-Cell Lymphoma. Blood 100(11): Abstract No 4693, November 16

The International Prognostic Index (IPI) identifies poor and good-risk patients with diffuse large B-cell lymphomas (DLBCLs). However, the majority of patients have an intermediate IPI, with an uncertain prognosis. Expression of P53 protein has been described in 13-70% of DLBCLs. P21 is transcriptionally activated by wild-type but not mutant P53 protein and serves as a mediator of the cell cycle arrest function of p53 gene via the inhibition of cyclin depend kinase (CDK). P53+/P21- cases are more likely to have a mutation and are also being expected to have a less favorable outcome. Thus, combined expression of P53 and P21 proteins can be used to predict p53 gene mutation. This data also can be used with IPI to predict survival in DLBCLs, mostly in the intermediate group. We studied diagnosis tumor samples from 51 patients with DLBCL for P53 and P21 expression by immunohistochemistry and p53 gene mutation status. Median survival was 16 months (varying from 5 to 129). 53% of all cases were P53+ (>=10%) and 14% of cases were P21+ (>=10%). We found 5 mutations in 4 patients (2 in exon 5, 1 in exon 6, 1 in exon 7, 1 in exon 8 of p53 gene). When patients were separated in three distinct groups (P53+/P21+, P53+/P21-, P53+/P21+ or -), Kaplan-Meier survival analysis curves using log-rank test showed significant difference in overall survival (p = 0.0372) and disease-free survival (p = 0.0306). Our results are in agreement with recent publications suggesting that P53+/P21- DLBCL have the worse prognosis and this is the most frequent phenotype related to p53 gene mutations. These simple immunohistochemistry techniques can be added to IPI to define survival, mainly in intermediate group.

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