TP53 Immunostaining in Double-Hit and Double-Expressing High-Grade B-Cell Lymphoma

Background: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma, but comprises a heterogenous group. Recent studies have identified aggressive subsets of DLBCL including double-hit lymphomas (DHL, with rearrangements of both MYC and BCL2 oncogenes and often classified in a separate DLBCL/Burkitt overlap category) and double-expressing lymphomas (DEL, which overexpress both MYC and BCL2). These subsets respond poorly to standard R-CHOP chemotherapy and account for most of the mortality associated with DLBCL. While recent studies have associated TP53 protein overexpression with worse prognosis in DLBCL, the effect of TP53 aberrations on these more aggressive DLBCL subsets is still uncertain.

Design: We performed a retrospective single institution analysis of a cohort of 26 DHL and a cohort of 65 R-CHOP-treated DLBCL, including 10 DEL. We recorded clinical information, treatment, and patient outcome. The DHL cases were treated with either R-CHOP or a more intensive regimen. A tissue microarray or recuts from original blocks were used for immunostains for TP53, BCL2, MYC, and cell-of-origin determination by Hans algorithm, which were scored blindly.

Results: TP53 expression (>10% of tumor cells) was significantly associated with higher expression of BCL2 (p=0.02), MYC (p=0.0009), and DEL status (p=0.005) in the DLBCL group. With respect to the association of DEL with TP53 expression, 7/10 (70%) cases of DEL were TP53+ compared to 10/55 (18%) of non-DEL DLBCL. There was no association with TP53 expression and cell-of-origin. No statistically significant difference in overall or relapse free survival between TP53+ and TP53- cases was identified in either cohort.

Conclusion: The findings in this small sample suggest that the relationship between TP53 staining and DLBCL outcome is more complex than previously reported, and may reflect an association of TP53 expression with DEL. The use of intensified treatment regimens (such as R-EPOCH) in the DHL cohort may abrogate any negative effects of TP53 overexpression in the TP53+ subset.