MYC and BCL2 protein expression predicts survival in patients with diffuse large B‐cell lymphoma treated with rituximab

Abstract

SummaryDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0Á015 and P = 0Á005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0Á001) and EFS (P = 0Á0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.

Scoring of MYC protein expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists

“…Prior studies indicated that discrepant cases were resolved through group review at multi-headed microscope but did not provide any further details. 9,10,13 As staining heterogeneity is the most significant factor causing discrepancy, specific instructions on how to address this problem are needed to improve concordance.…”

“…[9][10][11][12][13] These studies have shown that cases of diffuse large B-cell lymphoma with concurrent overexpression of MYC and BCL2 proteins have a dismal prognosis similar to those with double-hit lymphomas. The rate of so-called double-hit lymphoma-like cases as determined by immunohistochemistry is larger than the one detected by FISH.…”

“…[9][10][11][12][13] Tissue microarrays sample only a small portion of the tumor and therefore may underrepresent the heterogeneity of staining among tumor cells encountered in daily practice. The heterogeneity of MYC protein staining is not adequately addressed in these studies.…”

“…The heterogeneity of MYC protein staining is not adequately addressed in these studies. Additionally, the concordance rate is assessed among only two 10,11,13 or three 9 pathologists that might underestimate inter-observer variability among practicing pathologists. We hypothesized that these concordance rates might not be reproducible in daily practice.…”

Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

“…5,13,[22][23][24] Furthermore, the poor prognosis associated with Myc overexpression was contributed by cases with Myc/Bcl-2 coexpression-'doublepositive lymphoma' (DPL)-which account for 18-44% of DLBCLs. 13,20,[23][24][25][26] However, one study showed that the prognostic value of double-positive lymphoma was lost in younger DLBCL patients with poor prognosis. 27 Inconsistent results have been reported regarding whether the prognostic significance of Myc or Myc/Bcl2 protein expression depends on MYC or MYC/BCL2 gene rearrangement status or not.…”