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-ce ll lymphoma (ALCL), results in the production of the nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) protein. This repo rt describes an immuno-cytochemical study of the distribution of ALK a nd NPM-ALK proteins using a new monoclonal antibody, ALK1, that recogn izes a formalin resistant epitope in both the 80-kD NPM-ALK chimeric a nd the 200-kD normal human ALK proteins. Cytoplasmic and nuclear label ing was seen in the t(2;5)(+) SU-DHL-1 and Karpas 299 cell lines. Norm al ALK protein expression was restricted to the central nervous system (in scattered neurons, glial cells, and endothelial cells). Two hundr ed and thirty-nine cases of lymphoma and 80 nonhematopoietic tumors we re 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(+). Thre e cases of CD30(-) ALCL with prominent nucleoli showed a unique patter n of coarse granular cytoplasmic labeling, All other tumors, including Hodgkin's disease and lymphomatoid papulosis, were ALK1(-). These res ults indicate that reliable immunostaining of routine biopsy material for NPM-ALK and ALK proteins is feasible, Such analysis is of diagnost ic importance, especially because t(2;5)(+) ALCL cases have a good pro gnosis with appropriate treatment. (C) 1997 by The American Society of Hematology.