Expression of cell adhesion molecules and chemokine receptors: Angioinvasiveness in nasal NK/T-cell lymphoma

Abstract

Sinonasal natural killer (NK)/T-cell lymphoma (NKTCL) is closely associated with Epstein-Barr virus (EBV) infection and expresses latent membrane protein (LMP)-1 and EB nuclear antigen (EBNA)-1, i.e., latency II of EBV infection. Angioinvasion by neoplastic cells is a characteristic feature of NKTCL, but its mechanism is unknown. To elucidate the molecular mechanism of angio-invasiveness in NKTCL, expression of cell adhesion molecules and chemokine receptors at mRNA and protein levels was examined using real-time PCR and immunohistochemistry in 17 NKTCL together with 10 diffuse large B-cell lymphoma (DLBL) and 9 non-neoplastic nasal mucosa as controls. EBV DNA was detected in 14 of 16 NKTCL examined, and 7 of these 14 expressed LMP-1. mRNA expression levels of integrin subunits α4, αL, αM, and β2 were significantly higher in NKTCL than non-neoplastic controls. Integrin subunits α2 and αM were expressed at a significantly higher level in NKTCL with angioinvasion than those without. Expression level of αM was significantly higher in 7 cases of NKTCL with LMP-1 expression than 7 without. Immunohistochemistry showed expression of these molecules in NKTCL cells. These findings suggest that EBV infection might be involved in the pathogenesis of angioinvasion of NKTCL through up-regulation of αM by LMP-1.