BCL2 expression is associated with a poor prognosis independent of cellular origin in primary central nervous system diffuse large B-cell lymphoma
Primary central nervous system diffuse large B-cell lymphoma (CNS-DLBCL) is a distinct clinicopathological entity with a poor prognosis. Concurrent MYC and BCL2 overexpression predicts inferior prognosis in systemic DLBCL, although their prognostic significance remains unclear in primary CNS-DLBCL.
Pretreatment diagnostic biopsy samples were retrospectively evaluated for 79 patients with primary CNS-DLBCL who were treated between January 2001 and December 2017. Histological and immunohistochemical testing were performed to evaluate the patients’ statuses for various markers, which were also evaluated for associations with survival outcomes.
According to the Hans criteria, 26 patients (32.9%) had the germinal center B-cell subtype and 53 patients (67.1%) had the activated B-cell subtype. Forty-one cases (51.9%) were positive for MYC (expression of ≥ 40%), 33 cases (41.8%) were positive for BCL2 (expression of ≥ 70%), 22 patients (27.8%) were positive for both MYC and BCL2, and 27 patients (34.2%) were negative for both MYC and BCL2. There were no significant differences in survival between the germinal center and activated B-cell subtypes. Furthermore, MYC positivity was not associated with overall survival (p = 0.369) or progression-free survival (PFS) (p = 0.253). However, BCL2 positivity was significantly associated with poor overall survival (p = 0.039) and PFS (p = 0.036). Co-expression of MYC and BCL2 was not associated with survival.
Our data suggest that evaluating BCL2 expression may help predict the prognosis in cases of primary CNS-DLBCL.
KeywordsPrimary central nervous system lymphoma MYC BCL2 Immunohistochemistry Cell of origin
We thank Ms. Masayo Obata for her histological assistance.
This work was supported by Grants-in-Aid for Scientific Research(C) to KM (17K10870).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 10.Snuderl M, Kolman OK, Chen YB et al (2010) B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma. Am J Surg Pathol 34:327–340CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Hu S, Xu-Monette ZY, Tzankov A et al (2013) MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood 121:4021–4031CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Visco C, Li Y, Xu-Monette ZY et al (2012) Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia 26:2103–2113CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Nyman H, Adde M, Karjalainen-Lindsberg ML, Taskinen M, Berglund M, Amini RM, Blomqvist C, Enblad G, Leppa S (2007) Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood 109:4930–4935CrossRefPubMedGoogle Scholar
- 25.Lin CH, Kuo KT, Chuang SS, Kuo SH, Chang JH, Chang KC, Hsu HC, Tien HF, Cheng AL (2006) Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin. Clin Cancer Res 12:1152–1156CrossRefPubMedGoogle Scholar
- 26.Hattab EM, Martin SE, Al-Khatib SM, Kupsky WJ, Vance GH, Stohler RA, Czader M, Al-Abbadi MA (2010) Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases. Mod Pathol 23:235–243CrossRefPubMedGoogle Scholar
- 31.Brunn A, Nagel I, Montesinos-Rongen M et al (2013) Frequent triple-hit expression of MYC, BCL2, and BCL6 in primary lymphoma of the central nervous system and absence of a favorable MYC(low)BCL2 (low) subgroup may underlie the inferior prognosis as compared to systemic diffuse large B cell lymphomas. Acta Neuropathol 126:603–605CrossRefPubMedGoogle Scholar
- 33.Kim S, Nam SJ, Kwon D, Kim H, Lee E, Kim TM, Heo DS, Park SH, Kim CW, Jeon YK (2016) MYC and BCL2 overexpression is associated with a higher class of Memorial Sloan-Kettering Cancer Center prognostic model and poor clinical outcome in primary diffuse large B-cell lymphoma of the central nervous system. BMC Cancer 16:363CrossRefPubMedPubMedCentralGoogle Scholar