Expression of Survival Signals of Endoplasmic Reticulum Stress in Hodgkin Lymphoma
KC Chang, WC Chen, YT Jin, PCH Chen, D Jones. National Cheng Kung University, Tainan, Taiwan; Veterans General Hospital-Taipei, Taipei, Taiwan; University of Texas M.D. Anderson Cancer Center, Houston
Background: Hodgkin lymphoma (HL), originated from germinal center B cells, is associated with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein 1 (LMP1) rescues and reprograms germinal center B cells towards a Reed-Sternberg cell-like phenotype. In addition, LMP1 induces endoplasmic reticulum (ER) stress-related unfolded protein responses in EBV-infected B cells.
Design: To test the expression of ER stress signals (PERK, GRP78, XBP1, CHOP) in HL and the association with EBV, 156 cases of HL were analyzed by immunohistochemistry and EBV in situ hybridization.
Results: ER stress survival signals (GRP78 and XBP1 in 49% and 34% of cases, respectively) were expressed in all histologic subtypes of HL and in both EBV-positive and negative cases at a similar level. In contrast, HL rarely expressed ER death signal (CHOP, 9%). There was agreement of EBV in situ hybridization with LMP1 stain (p < 0.0001) and GRP78 with XBP1 expression (p = 0.006). In vitro LMP1 transfection increased expression of GRP78 and XBP1 in HL cell line. Expression of ER signals did not bear prognostic significance.
Conclusions: It implies that near half cases of HL adapted and survived ER stress, which may be associated with overexpression of LMP1 and may be a decision-making step accounting for the relatively rare occurrence of HL in more prevalent EBV infection.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 197, Wednesday Morning