Clinicopathologic and Prognostic Significance of Bruton's Tyrosine Kinase Expression in Diffuse Large B-Cell Lymphoma

Autor: Jong Seok Lee, Jeong Ok Lee, Hyun Jung Kwon, Jeong Mi Yang, Jin Ho Paik, Yeon Bi Han
Rok vydání: 2021
Předmět:
Adult
Male
Cancer Research
Vincristine
Cyclophosphamide
Adolescent
Proto-Oncogene Mas
Risk Assessment
Translocation
Genetic
Proto-Oncogene Proteins c-myc
Young Adult
International Prognostic Index
immune system diseases
Predictive Value of Tests
Risk Factors
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
medicine
Agammaglobulinaemia Tyrosine Kinase
Biomarkers
Tumor
Bruton's tyrosine kinase
Humans
Protein Kinase Inhibitors
In Situ Hybridization
Fluorescence
Aged
Retrospective Studies
Aged
80 and over
biology
business.industry
Gene Amplification
General Medicine
Middle Aged
medicine.disease
Immunohistochemistry
Progression-Free Survival
Lymphoma
Oncology
Proto-Oncogene Proteins c-bcl-2
Drug Resistance
Neoplasm
Cancer research
biology.protein
Rituximab
Female
Lymphoma
Large B-Cell
Diffuse
business
Diffuse large B-cell lymphoma
Tyrosine kinase
medicine.drug
Zdroj: Anticancer research. 41(11)
ISSN: 1791-7530
Popis: BACKGROUND/AIM Bruton's tyrosine kinase (BTK)-mediated B-cell-receptor signaling drives lymphomagenesis of diffuse large B-cell lymphoma (DLBCL). We investigated the clinicopathological significance of BTK positivity in DLBCL according to known molecules related to resistance to BTK inhibitors [BCL2 apoptosis regulator (BCL2)/MYC proto-oncogene, bHLH transcription factor (MYC)]. PATIENTS AND METHODS We evaluated BTK expression immunohistochemically in 106 DLBCLs considering their BCL2/MYC status. RESULTS Considering the whole cohort, BTK was expressed in 65.1%, including 70.4% (50/71) of non-germinal center B-cell-like (non-GCB) subtype; BCL2 expression was detected in 60.4%, MYC expression in 15.1%, MYC translocation in 4.2% (4/96) and MYC gain/amplification in 7.6% (8/105). Overall and in the non-GCB cohort, BTK positively correlated with high international prognostic index (both p=0.005) and stage (p=0.006 and p=0.002), and with BCL2 intensity (p=0.005 and p=0.026, respectively); MYC gain/amplification total cohort (p=0.038). Moreover, high risk, defined as co-expression of BTK and either or both BCL2/MYC, independently predicted shorter progression-free survival in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) (all R-CHOP-treated patients: hazard ratio=2.565, p=0.044; R-CHOP-treated non-GCB subgroup: HR=3.833, p=0.019). CONCLUSION BTK expression may be utilized to stratify risk in patients with DLBCL.
Databáze: OpenAIRE
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