Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1

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 immuno-cytochemical 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. (C) 1997 by The American Society of Hematology.