The Clinicopathological Features of Anaplastic Large Cell Lymphomas Expressing p80NPM/ALK

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Abstract
The classification of malignant lymphoma has been based on morphological and immunophenotypical findings for a long time. Recently, as chromosomal and genomic abnormalities which closely relate to the specific subtypes of lymphoma are revealed, these factors becoming much more important in the evaluation of differences in clinicopathological features of the various lymphoma subtypes. Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma (NHL) involving large CD30+ neoplastic cells, which occasionally carries the chromosomal translocation t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kDa protein tyrosine kinase, p80 which is expressed specifically in human ALCLs with this translocation. Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene. In order to clarify the clinicopathologic features of p80-carrying ALCLs, we developed an anti-p80 polyclonal antibody, which immunoprecipitated, immunoblotted and immunostained p80 specifically. When paraffin sections of 105 cases of ALCL were stained using the anti-p80 antibody, 30 were shown to be p80 positive Clinicopathological comparison between p80-positive and p80-negative ALCLs revealed that the p80-positive cases occurred in a much younger patient age group and that the patients showed a far better 5-year survival rate. These data suggest that p80-positive ALCL is a distinct entity and should be differentiated from p80-negative ALCL.