title: Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1.
abstract: The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the production of the nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) protein. This report describes an immunocytochemical study of the distribution of ALK and NPM-ALK proteins using a new monoclonal antibody, ALK1, that recognizes a formalin resistant epitope in both the 80-kD NPM-ALK chimeric and the 200-kD normal human ALK proteins. Cytoplasmic and nuclear labeling was seen in the t(2;5)+ SU-DHL-1 and Karpas 299 cell lines. Normal ALK protein expression was restricted to the central nervous system (in scattered neurons, glial cells, and endothelial cells). Two hundred and thirty-nine cases of lymphoma and 80 nonhematopoietic tumors were immunostained. Antibody ALK1 labeled 53.4% (39 of 73 cases) of CD30+ ALCL. A case of ALCL with a t(1;2) translocation was ALK1+. Three cases of CD30- ALCL with prominent nucleoli showed a unique pattern of coarse granular cytoplasmic labeling. All other tumors, including Hodgkin's disease and lymphomatoid papulosis, were ALK1-. These results indicate that reliable immunostaining of routine biopsy material for NPM-ALK and ALK proteins is feasible. Such analysis is of diagnostic importance, especially because t(2;5)+ ALCL cases have a good prognosis with appropriate treatment.
authors.affiliation: University Department of Cellular Science, John Radcliffe Hospital, Oxford, UK.
authors.forename: K
authors.initials: K
authors.lastname: Pulford
authors.forename: L
authors.initials: L
authors.lastname: Lamant
authors.forename: S W
authors.initials: SW
authors.lastname: Morris
authors.forename: L H
authors.initials: LH
authors.lastname: Butler
authors.forename: K M
authors.initials: KM
authors.lastname: Wood
authors.forename: D
authors.initials: D
authors.lastname: Stroud
authors.forename: G
authors.initials: G
authors.lastname: Delsol
authors.forename: D Y
authors.initials: DY
authors.lastname: Mason
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000235:genetics; D003937:Diagnosis, Differential; D005240:Feasibility Studies; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis / Q000201:enzymology; D006801:Humans; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000201:enzymology* / Q000648:ultrastructure; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000201:enzymology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000090243:Nucleophosmin; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases