Figure 5

EBV Hodgkin lymphomas is associated with suppression of p21^cip1/waf1 and a worse prognosis. 5A: Immunohistochemistry of p21^cip1/waf1. Upper panel from left to right: K9, L9, and an EBV^— HL were positive for p21^cip1/waf1. Lower panel from left to right: KE, LE, and an EBV⁺ HL were negative for p21^cip1/waf1. Immunoperoxidase stains on formalin-fixed, paraffin-embedded cell blocks or tissue sections. 5B: The EBV⁺ group also had a worse 2-year OS rate than did the EBV^— group (68% vs. 98%, p < 0.001 by logrank test). 5C: The EBV⁺ group had a worse 2-year DFS rate than did the EBV^— group (45% vs. 77%, p = 0.002 by logrank test). 5D: EBER1 inhibits apoptosis and maintains latency through p21^cip1/waf1 suppression (Arrow: increase; Bar: decrease). Our data are consistent with the model that EBER1 could inhibit p21^cip1/waf1 transcription through EGR1, STAT1, or p53. The inhibition of p21^cip1/waf1 is associated with resistance to drug-induced apoptosis. Because p21^cip1/waf1 is necessary for lytic induction by EBV-encoded ZTA [36, 37], EBER1 may be critical for the maintenance of the latency phase as well. Since the binding sites on the p21^cip1/waf1 promoter for EGR1 [18, 19], STAT1 [20], and p53 [21, 22] are already known, further studies are necessary to reveal how EBER1 suppresses p53, EGR1, and STAT1, and whether or not post-transcriptional regulations of p21^cip1/waf1 are also involved.