Contributions
Abstract: PB1431
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Diffuse large B-cell lymphoma (DLBCL) is one of the most common, aggressive, clinically and biologically heterogeneous B-cell neoplasms. Impaired cell differentiation, maturation, and proliferation of B lymphoid elements are the main components of the disease pathogenesis. Protein p53 encoded by the TP53 gene is the key tumor suppressor that holds the cell cycle, enables DNA reparation and apoptosis. Disruption of the structure and functions of this transcription factor in DLBCL patients is caused by various mechanisms, including mutations in TP53 exons, deletions of chromosome 17p13 locus, abnormal p53 promoter methylation, etc. Inactivation of certain pro-apoptotic genes or hyperactivation of anti-apoptotic mechanisms can also affect p53 functions. Many researchers agree that TP53 mutations and immunohistochemical (IHC) protein p53 expression in tumor cells are important factors that have an impact on the prognosis of DLBCL. However, studies investigating their relationship are few and contradicting, which confirms the relevance of this study.
Aims
To evaluate the relationship between genetic aberrations in the 17p13/TP53 locus and IHC protein p53 expression in tumor cells in patients with DLBCL.
Methods
The study included a total of 75 patients aged from 30 to 82 years (median age: 58 years) with newly diagnosed DLBCL who received treatment at the clinic of the Institute. All patients received R-CHOP as a first-line treatment. The deletion of the 17p13/TP53 locus was determined by fluorescence in situ hybridization (FISH) in biopsy specimens of tumor tissue using the Kreatech TP53 (17p13) / SE 17 FISH probes. The relative number of p53-expressing tumor cells was calculated by IHC and morphometry. The threshold value of IHC p53 expression was evaluated by ROC analysis. The association between 17р13/ТР53 deletion and protein p53 expression in tumor cells was evaluated using Fisher’s exact test (F). The correlation was evaluated using Cramer’s rule (V).
Results
Deletions of the 17р13/ТР53 locus were detected in 8 (11%) of 75 DLBCL patients. ROC analysis showed that the threshold value of IHC expression of p53-positive cells was 43%. This value was used to determine marker hyperexpression (≥ 43% of tumor cells) in 33 (44%) of subjects. The percentage of expressive cells in the remaining patients was lower than the threshold value. The incidence of 17p13 deletions was significantly higher in patients with p53 hyperexpression than in patients with protein p53 levels below the threshold value: 87.5% vs. 12.5%, respectively (р=0.018; OR=11.04). A correlation between 17р13/ТР53 deletion and protein p53 expression in tumor cells (р=0.018; V=0.3) was established.
Conclusion
17р13/ТР53 deletions in DLBCL patients are associated with suprathreshold IHC protein p53 expression in tumor cells. A direct moderate correlation has been established between these laboratory values.
Keyword(s): Diffuse large B cell lymphoma, P53
Abstract: PB1431
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Diffuse large B-cell lymphoma (DLBCL) is one of the most common, aggressive, clinically and biologically heterogeneous B-cell neoplasms. Impaired cell differentiation, maturation, and proliferation of B lymphoid elements are the main components of the disease pathogenesis. Protein p53 encoded by the TP53 gene is the key tumor suppressor that holds the cell cycle, enables DNA reparation and apoptosis. Disruption of the structure and functions of this transcription factor in DLBCL patients is caused by various mechanisms, including mutations in TP53 exons, deletions of chromosome 17p13 locus, abnormal p53 promoter methylation, etc. Inactivation of certain pro-apoptotic genes or hyperactivation of anti-apoptotic mechanisms can also affect p53 functions. Many researchers agree that TP53 mutations and immunohistochemical (IHC) protein p53 expression in tumor cells are important factors that have an impact on the prognosis of DLBCL. However, studies investigating their relationship are few and contradicting, which confirms the relevance of this study.
Aims
To evaluate the relationship between genetic aberrations in the 17p13/TP53 locus and IHC protein p53 expression in tumor cells in patients with DLBCL.
Methods
The study included a total of 75 patients aged from 30 to 82 years (median age: 58 years) with newly diagnosed DLBCL who received treatment at the clinic of the Institute. All patients received R-CHOP as a first-line treatment. The deletion of the 17p13/TP53 locus was determined by fluorescence in situ hybridization (FISH) in biopsy specimens of tumor tissue using the Kreatech TP53 (17p13) / SE 17 FISH probes. The relative number of p53-expressing tumor cells was calculated by IHC and morphometry. The threshold value of IHC p53 expression was evaluated by ROC analysis. The association between 17р13/ТР53 deletion and protein p53 expression in tumor cells was evaluated using Fisher’s exact test (F). The correlation was evaluated using Cramer’s rule (V).
Results
Deletions of the 17р13/ТР53 locus were detected in 8 (11%) of 75 DLBCL patients. ROC analysis showed that the threshold value of IHC expression of p53-positive cells was 43%. This value was used to determine marker hyperexpression (≥ 43% of tumor cells) in 33 (44%) of subjects. The percentage of expressive cells in the remaining patients was lower than the threshold value. The incidence of 17p13 deletions was significantly higher in patients with p53 hyperexpression than in patients with protein p53 levels below the threshold value: 87.5% vs. 12.5%, respectively (р=0.018; OR=11.04). A correlation between 17р13/ТР53 deletion and protein p53 expression in tumor cells (р=0.018; V=0.3) was established.
Conclusion
17р13/ТР53 deletions in DLBCL patients are associated with suprathreshold IHC protein p53 expression in tumor cells. A direct moderate correlation has been established between these laboratory values.
Keyword(s): Diffuse large B cell lymphoma, P53