Contributions
Abstract: PB1432
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Currently, a number of clinical stratification systems (international prognostic indexes, staging, and others) are used to determine the prognosis of the disease. However, they do not accurately assess the individual risk of therapy failure. In this regard, it is of interest to search for additional biological criteria that determine the prognosis of the disease.
Dysregulation of key molecules (pAKT1, pSyk) of the PI3K / AKT / mTOR and BCR signaling pathways affects the biological characteristic of tumor cells and may determine the prognosis of DLBCL. It is known that monotypic overexpression of pAKT1 and pSyk is associated with low overall (OS) and рrogression-free survival (PFS) in DLBCL patients; however, the combined expression of these proteins in this pathology has not been studied, which emphasizes the relevance of the study.
Aims
To assess the association of the co-expression of the pAKT1 and pSyk proteins in tumor cells with OS and PFS in DLBCL patients.
Methods
As a material for the study, FFPE samples of lymph nodes and other organs and tissues were used, obtained from 100 patients with a newly diagnosed DLBCL who were treated at the clinic of the KRIHBT in the period from 2012 to 2018. All patients received standard first-line immunochemotherapy according to the R-CHOP regimen. The determination of the relative number of tumor cells expressing pAKT1, pSyk was carried out using immunohistochemical and morphometric methods. OS and PFS were calculated by the Kaplan-Meier method using the log-rank test. The cutoff for expression of these proteins was calculated using the ROC analysis: for pAKT1 was set at 70% of positive tumor cells, for pSyk - 28%. According to the established thresholds, all subjects were divided into groups with high [≥70% (+) for pAKT1; ≥28% (+) for pSyk] and low [<70% (-) for pAKT1; <28% (-) for pSyk] by expression of the indicated proteins. The interrelation between different variants of pAKT1 and pSyk co-expression with the course of DLBCL was analyzed.
Results
The highest OS (90.2%) was recorded in the group of patients (n=41) with low coexpression of markers (pAKT1-/pSyk -). In the presence of coexpressions of pAKT1+/pSyk- and pAKT1-/pSyk+, it was 52% (n=29 ) and 60% (n=15), respectively. The lowest values of OS (26.7%) were observed in patients (n=15) with the combination of pAKT1+/pSyk+, which significantly differed from other variants of co-expression of markers (p<0.001; HR=5.2; 95% CI=2.49-10.9).
A similar pattern was established in the analysis of PFS. The proportion of patients without disease progression with the variant of co-expression of pAKT1 - / pSyk- was 78.1% (n=41), and in the presence of combinations of rACT1+/pSyk - and rACT1-/pSyk+ - 55% (n=29) and 53% (n=15), respectively. The lowest level of PFS (40%) was registered in patients with simultaneous overexpression of markers (n=15; p=0.002; HR=3.3; 95% CI=1.54-7.30).
Conclusion
Conclusion. Combined overexpression of the pAKT1 and pSyk biomarkers is associated with a more unfavorable prognosis of DLBCL compared to other variants of their coexpression.
Keyword(s): DLBCL, Survival
Abstract: PB1432
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Currently, a number of clinical stratification systems (international prognostic indexes, staging, and others) are used to determine the prognosis of the disease. However, they do not accurately assess the individual risk of therapy failure. In this regard, it is of interest to search for additional biological criteria that determine the prognosis of the disease.
Dysregulation of key molecules (pAKT1, pSyk) of the PI3K / AKT / mTOR and BCR signaling pathways affects the biological characteristic of tumor cells and may determine the prognosis of DLBCL. It is known that monotypic overexpression of pAKT1 and pSyk is associated with low overall (OS) and рrogression-free survival (PFS) in DLBCL patients; however, the combined expression of these proteins in this pathology has not been studied, which emphasizes the relevance of the study.
Aims
To assess the association of the co-expression of the pAKT1 and pSyk proteins in tumor cells with OS and PFS in DLBCL patients.
Methods
As a material for the study, FFPE samples of lymph nodes and other organs and tissues were used, obtained from 100 patients with a newly diagnosed DLBCL who were treated at the clinic of the KRIHBT in the period from 2012 to 2018. All patients received standard first-line immunochemotherapy according to the R-CHOP regimen. The determination of the relative number of tumor cells expressing pAKT1, pSyk was carried out using immunohistochemical and morphometric methods. OS and PFS were calculated by the Kaplan-Meier method using the log-rank test. The cutoff for expression of these proteins was calculated using the ROC analysis: for pAKT1 was set at 70% of positive tumor cells, for pSyk - 28%. According to the established thresholds, all subjects were divided into groups with high [≥70% (+) for pAKT1; ≥28% (+) for pSyk] and low [<70% (-) for pAKT1; <28% (-) for pSyk] by expression of the indicated proteins. The interrelation between different variants of pAKT1 and pSyk co-expression with the course of DLBCL was analyzed.
Results
The highest OS (90.2%) was recorded in the group of patients (n=41) with low coexpression of markers (pAKT1-/pSyk -). In the presence of coexpressions of pAKT1+/pSyk- and pAKT1-/pSyk+, it was 52% (n=29 ) and 60% (n=15), respectively. The lowest values of OS (26.7%) were observed in patients (n=15) with the combination of pAKT1+/pSyk+, which significantly differed from other variants of co-expression of markers (p<0.001; HR=5.2; 95% CI=2.49-10.9).
A similar pattern was established in the analysis of PFS. The proportion of patients without disease progression with the variant of co-expression of pAKT1 - / pSyk- was 78.1% (n=41), and in the presence of combinations of rACT1+/pSyk - and rACT1-/pSyk+ - 55% (n=29) and 53% (n=15), respectively. The lowest level of PFS (40%) was registered in patients with simultaneous overexpression of markers (n=15; p=0.002; HR=3.3; 95% CI=1.54-7.30).
Conclusion
Conclusion. Combined overexpression of the pAKT1 and pSyk biomarkers is associated with a more unfavorable prognosis of DLBCL compared to other variants of their coexpression.
Keyword(s): DLBCL, Survival