Clinicopathologic and Prognostic Significance of Bruton's Tyrosine Kinase Expression in Diffuse Large B-Cell Lymphoma.
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.
['Han|Yeon Bi|YB|', 'Yang|Jeong Mi|JM|', 'Kwon|Hyun Jung|HJ|', 'Lee|Jeong-Ok|JO|', 'Lee|Jong Seok|JS|', 'Paik|Jin Ho|JH|']
D000293:Adolescent D000328:Adult D000077329:Agammaglobulinaemia Tyrosine Kinase D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D014408:Biomarkers, Tumor D019008:Drug Resistance, Neoplasm D005260:Female D005784:Gene Amplification D006801:Humans D007150:Immunohistochemistry D017404:In Situ Hybridization, Fluorescence D016403:Lymphoma, Large B-Cell, Diffuse D008297:Male D008875:Middle Aged D011237:Predictive Value of Tests D000077982:Progression-Free Survival D047428:Protein Kinase Inhibitors D000090063:Proto-Oncogene Mas D019253:Proto-Oncogene Proteins c-bcl-2 D016271:Proto-Oncogene Proteins c-myc D012189:Retrospective Studies D018570:Risk Assessment D012307:Risk Factors D014178:Translocation, Genetic D055815:Young Adult
diffuse large B-cell Lymphoma BCL2 Bruton’s tyrosine kinase c-MYC prognosis