Association of p53 protein expression with the presence of a 17p13 locus deletion of the TP53 gene and with the survival of patients with diffuse large B-cell lymphoma

Abstract

Background. A significant role in the pathogenesis, resistance to treatment and progression of many types of lymphomas, including diffuse large B-cell lymphoma, is assigned to the TP53 gene. Literature data on the prognostic significance of the expression of its product, the p53 protein, and its association with aberrations at the 17p13 locus are ambiguous.

Aim. To assess the relationship of p53 protein expression with the presence of a 17p13 locus deletion of the TP53 gene and the survival of patients with diffuse large B-cell lymphoma.

Material and methods. The study included 75 patients with newly diagnosed diffuse large B-cell lymphoma who received R-CHOP therapy. The calculation of the relative content of tumor cells expressing p53 was carried out using immunohistochemical and morphometric methods on biopsy samples of lymph nodes. The 17p13/TP53 deletion was determined by fluorescent in situ hybridization. The threshold level of p53-positive tumor cells, corresponding to 43%, was calculated by ROC analysis. The association between p53 protein expression and the presence of a 17p13 deletion was assessed using Fisher's (F) and Pearson's χ2 tests. The correlation dependence was evaluated by the Cramer method (V). Five-year overall and progression-free survival was calculated using the Kaplan–Meier method. Differences between the indicators were considered statistically significant at p <0.05.

Results. The frequency of 17p13/TP53 deletion was higher in patients with high expression of p53 (≥43%) compared to the group of patients with low expression: 87.5 and 12.5%, respectively (p=0.018). A direct correlation between a high level of p53 expression (>43%) and the presence of a 17p13/TP53 deletion was found (p=0.018). Five-year overall and progression-free survival in patients with a proportion of p53-positive cells> 43% was significantly lower than in patients with its subthreshold value: 54.5 versus 81.0% (p=0.014) and 45.5 versus 66.7% (p=0.022), respectively.

Conclusion. High expression of the p53 protein is associated with the presence of a 17p13 locus deletion and a low five-year survival rate in patients with diffuse large B-cell lymphoma.

Keywords

TP53 / p53 / DLBCL / survival / IHC

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Funding

ФГБУН «Кировский научно-исследовательский институт гематологии и переливания крови Федерального медико-биологического агентства»

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