Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma

Translocations affecting both MYC and BCL2 are associated with a poor prognosis in diffuse large B-cell lymphomas. We have examined genetic aberrations combined with analyses of protein expression of respective gene products. Fluorescence in situ hybridization (FISH) for translocations of BCL2 and MYC and del17p13 was performed. Immunohistochemistry analyses included BCL2, MYC and TP53 protein expression. Sixty-seven patients with high-risk DLBCL participating in a prospective multicenter study were included. Six patients with simultaneous translocations of BCL2 and MYC had impaired overall (OS) (p = 0.009) and progression-free survival (PFS) (p= 0.009). Six patients with high coexpression of MYC and BCL2 proteins also had impaired OS (p = 0.004) and PFS (p = 0.002). Combining these groups identified nine patients with impaired OS (p= 0.004) and PFS (p= 0.005). Sixteen patients had double-hit translocation or protein expression and/or del17p13 and/or high TP53. This combined endpoint was associated with impaired OS (p= 0.008) and PFS (p= 0.036), and identified 70% of all deaths.