P53 expression correlates with poorer survival and augments the negative prognostic effect of MYC rearrangement, expression or concurrent MYC/BCL2 expression in diffuse large B-cell lymphoma

Abstract

In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53. Compared with patients with P53 negative lymphoma, the P53 positive group had a poorer overall survival (P=0.004). In patients with lymphoma harboring MYC-R, MYC expression or MYC+/BCL2+, P53 expression was associated with a significantly worse overall survival (P<0.0001, P=0.01, and P=0.035, respectively). Patients with lymphoma showing concurrent P53 expression and MYC-R had a worse prognosis compared with patients with either P53 expression or MYC-R alone (P<0.0001). Similarly, P53 enhanced the negative prognostic effect of MYC expression in DLBCL patients. In addition, among patients with lymphoma with concurrent MYC and P53 expression, MYC and BCL2 or BCL2 & P53 expression, those patients with tumors with MYC and P53 expression had the worst overall survival (P=0.005), regardless of BCL2 expression status. Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC -R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novo diffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas

“…The cutoffs for CD10, BCL6, and MUM1 positivity were 30% as used in the Hans algorithm [26]. The positive cutoffs for MYC, BCL2, and P53 expression were ≥40%, ≥50%, and ≥50% of cells, respectively, as have been reported previously [21,[27][28][29][30][31].…”

“…Previous studies have shown that P53 expression can enhance the negative effect of MYC translocation and expression [40,41]. In earlier studies, P53 overexpression was shown to augment the negative prognostic effect of MYC/BCL2 double hit lymphoma and MYC/BCL2 double expression lymphoma [28,30]; in other words, P53 expression is a poor prognostic factor in MYC/BCL2 double hit lymphoma. In this study, P53 expression was observed in 29% of triple hit lymphoma cases evaluated and was associated with an inferior overall survival compared to cases without P53 overexpression (p = 0.04), similar to the negative impact of P53 reported in MYC/ BCL2 double hit lymphoma.…”

“…3d, p < 0.0001). Since P53 expression is a prognostic factor in triple hit lymphoma as well as in double hit lymphoma [30], further survival analyses were performed to compare the survival of triple hit lymphoma patients to double hit lymphoma patients when P53 < 50%, and still showed no survival difference between them (Fig. 3e).…”

Double hit and double expressors in lymphoma: Definition and treatment

“…8 MYC can also paradoxically lead to the repression of apoptosis by increasing the expression of the tumor suppressor TP53. [9][10][11] To overcome this scenario, MYC requires the contribution of other genetic events (eg, the expression of BCL2 and mutations in TP53) to promote Cancer December 15, 2018 proliferation and oncogenesis. 8 The spectrum of MYC effects appears dependent on the histologic context; for example, transcriptional targets in Burkitt lymphoma (BL) are completely distinct from transcriptional targets in DLBCL even though they share an identical t (8;14) rearrangement.…”

EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53

“…Staining for p53 protein was uniformly strong in the tumor, correlating well with the presence of mutations. Expression of p53 in de novo DLBCL was shown to be correlated with inferior outcome [20, 21]. In addition to TP53 mutations, FISH studies of the patient's tumor showed deletion of TP53 in 14/100 cells and monosomy of chromosome 17 in 20/100 cells (Figure 3).…”