Portal de Periódicos da CAPES

“focus on…” session: T-cell

2008; Elsevier BV; Volume: 19; Linguagem: Inglês

10.1093/annonc/mdn221

1569-8041

Judit Jørgensen, Flemming Brandt Sørensen, Knud Bendix, Jens Cosedis Nielsen, Anette MD Funder, Marika J. Karkkainen, Tapio Tainola, Finn Skou Pedersen, Annette Balle Sørensen, A Ku ̈hle, Francesco d’Amore, Takashi Watanabe, T Kinoshita, K. Itoh, Kenji Yoshimura, Hideto Kaba, Monami Ogura, Yoshihiro Kagami, M Yamaguchi, M Kurosawa, Kunihiro Tsukasaki, M. Kasai, K Tobinai, K Mukai, Shota Nakamura, Kohichi Ohshima, Taeko Hotta, Masaaki Shimoyama,

Cancer Immunotherapy and Biomarkers

Background: EBV is known to be associated with various lymphoid malignancies.An up-regulation of VEGF by EBV has been suggested.The aim of this study was to investigate the correlation between the expression of EBER and angiogenic molecules in PTCL and to examine their possible prognostic impact.Material and methods: Tissue sections from 62 PTCL (36 PTCL-unspecified (PTCLu), 1 NK/T nasal type, 7 angioimmunoblastic (AIL), 18 anaplastic large cell (ALCL)) were analysed.The expressions of EBV encoded small nuclear RNAs (EBER) and VEGF mRNA were detected by in situ hybridization (ISH).The expression of LMP-1 protein was examined by immunohistochemistry (IH).In 44 cases, the expressions of VEGF, VEGF-C, Flt-1, KDR and Flt-4 were also estimated by IH.Results: EBER expression was detected in 37% of the all PTCL cases (PTCL-u 38 %, AIL 85%, ALCL 16%).Strong EBER positivity correlated to higher VEGF mRNA expression, both in the entire cohort analysed (p=0.02) and separately in PTCL-u (p=0.02).High EBER expression correlated to nuclear Flt-4 expression (p=0.01).Cases showing diffuse expression of VEGF mRNA had significantly poorer event-free (p=0.02) and overall (p=0.04)survival than cases with focal or no expression.Higher EBER expression was correlated with higher IPI (p=0.01), but had no impact on survival when all PTCL cases were analysed together.If analysed separately for PTCL-u, a high EBER expression predicted a poorer event-free survival (p=0.02) and tended to be associated with adverse impact on overall survival (p=0.08).Conclusions: EBV RNA was detected in 37% of all PTCL cases analysed.Strong EBER expression significantly correlated to higher VEGF mRNA and nuclear Flt-4 expression, suggesting that EBER may up-regulate angiogenic pathways in lymphoma cells.Diffuse VEGF expression was associated with an adverse impact on survival.In PTCL-u, EBER predicted poorer outcome.