title: Epstein-Barr virus association and ALK gene expression in anaplastic large-cell lymphoma.
abstract: Anaplastic large cell lymphoma of T/null-cell type (ALCL) is associated with a characteristic genetic abnormality t(2;5) that results in the NPM-ALK chimeric gene and the protein product derived thereof. In 10% to 20% of ALCLs, the translocation partners of the ALK gene are genes other than NPM (variant translocations). ALK gene expression limited to the cytoplasm implies a variant translocation. In this study, we have investigated 46 cases of ALCL for expression and localization of ALK protein and its association with Epstein-Barr virus (EBV) (by hybridization to EBV-encoded nuclear RNA-1 [EBER-1] and immunostaining for LMP-1). ALCL patients with a null cell phenotype were significantly younger as compared with those of T-cell phenotype (mean age: 28 years v 42 years; P =.018). Sixteen of 46 ALCL cases (34%) were ALK positive. ALK-positive patients were significantly younger (mean age: 25 years for those with both cytoplasmic and nuclear staining; 22 years for those with exclusive cytoplasmic staining; and 41 years for those negative for the ALK gene; P =.023). EBER-1 was detected in 9 of 46 cases (20%), and LMP-1 expression was noted in 5 of them. By polymerase chain reaction analysis, all EBV-associated cases that were investigated showed type I EBV. Whereas 2 of 23 T-cell ALCLs (9%) were EBER-1+, and 7 of 23 null-cell ALCLs (30%) showed EBV association (P =.057). EBV association was seen in 20% of ALK-negative cases, in 0% of cases with ALK gene expression in both nucleus and cytoplasm, and in 60% of cases with ALK gene expression exclusively in the cytoplasm (P =.02). Further, although ALK-positive-EBER-1+ cases were LMP-1 negative, ALK-negative-EBER-1+ cases were LMP-1 positive. Our study raises the question whether EBV might have an etiological role in the evolution of ALCLs that lack classical t(2;5).
authors.affiliation: Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Agarwal
authors.forename: Uma
authors.initials: U
authors.lastname: Ramanathan
authors.forename: Kikkerj N
authors.initials: KN
authors.lastname: Naresh
mesh_terms: D000328:Adult; D000367:Age Factors; D000077548:Anaplastic Lymphoma Kinase; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000821:virology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012367:RNA, Viral / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D013601:T-Lymphocytes; D014178:Translocation, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D014763:Viral Matrix Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases