PB1819 STAT3 PROTEIN AS A PROGNOSTIC FACTOR OF DIFFUSE LARGE B‐CELL LYMPHOMA
Authors: E. Vaneeva, V. Rosin, D. Dyakonov, S. Samarina, E. Poponina, A. Rylov, I. Paramonov
Journal: HemaSphere (2019)

Background: Diffuse large B‐cell lymphoma (DLBCL) is the most common type of non‐Hodgkin's lymphoma (NHL) in adults (30% to 40%). Nosology combines a heterogeneous group of lymphoid neoplasias with various morphological, immunophenotypic, genetic characteristics, as well as variable clinical course and response to therapy. The R‐CHOP regimen is considered the standard therapeutic option for diffuse large B‐cell lymphoma. Although combination chemotherapy has improved the outcome, many patients do not achieve complete remission, 5‐year overall survival (OS) for DLBCL patients ranges from 30% to 50%, the disease remains resistant to treatment or recurs in its early stages. The development of International Prognostic Indices (IPI, aaIPI and others) has provided with a wide range of criteria for predicting the evolution of aggressive lymphomas. However, they do not always allow evaluating the individual risk of treatment failure. In this regard, the search for additional criteria that determine the prognosis of the disease is of a large interest. STAT3 protein may be one of the promising biomarkers in DLBCL. This protein is an important member of the Janus kinase (JAK) and signal transducer and activator (JAK/STAT) pathway participators. Aberrant activation of STAT3 has been found in several tumors including DLBCL. The value of protein in this nosology has not been studied enough, the question of its prognostic role remains open. Aims: To determine the prognostic value of the expression of STAT3 protein in patients with DLBCL. Methods: The cohort consisted of 50 patients with de novo DLBCL treated with the standard R‐CHOP regimen from 2014 to 2017. Immunohistochemical studies used 2 μm thick tissue samples of the tumor, the antibody used STAT3 (pSTAT3‐Tyr705). Based on the literature data, the threshold value for the pSTAT3 marker were 66%. Patients were divided into two groups relative to the number of STAT3 positive tumor cells. The first group included 16 patients (32%) with a low degree of expression of the marker (less than 66% of the cells), the second ‐ 34 subjects (68%) with overexpression of the protein (66% and above). Overall and non‐progressive survival were analyzed by Kaplan–Meier method, with difference compared by the log‐rank test. Results: For cases of low STAT3 expression the OS was significantly higher than cases of high STAT3 expression (93,8% versus 41.2%, (p = 0.04)). The PFS for low and high STAT3 expression group was 50% and 38%, respectively, with statistical significance (p = 0.047). At the same time, the median survival without progression in the second group was 8 months, in the first group ‐ 26 months. Summary/Conclusion: Among the patients with DLBCL treated with the R‐CHOP protocol, overexpression of STAT3 protein is associated with an unfavorable course of the disease. The expression level of this marker can act as an additional prognostic criterion that determines the sensitivity of the tumor to standard therapy and allows personalizing the treatment tactics.