Expression of the NPM-ALK fusion protein in anaplastic lymphoma
Wood KM., Parr A., Jack F., Pulford K., Lessells AM., Krajewski AS., Levison DA., Goodlad J., Thompson WD., Lee FD., Angus B.
A proportion of anaplastic large cell lymphomas possess the translocation t(2;5)(p23;q35) which fuses the nucleophosmin (NPM) nucleolar phosphoprotein gene on 5q35 to the anaplastic lymphoma kinase (ALK) gene on 2p23, resulting in the expression of a novel NPM-ALK fusion protein. This can be detected immunohistochemically with the the monoclonal antibody ALK1. 49 cases of anaplastic lymphoma were induced in the study on the basis of CD30-positivity and anaplastic morphology. Immunostaining was performed with the ALK1 antibody and also for a panel of other antigens (CD20, CD79a, CD43, CD3, CD45RO, Epithelial Membrane-Antigen (EMA) and EBV LMH), on routinely processed paraffin sections. 11 cases were ALK1-positive (1 T-cell, 10 null). A further 23 T/null lymphomas were ALK1-negative. 15 B-cell lymphomas were ALK1-negative. ALK1-positivity was associated with EMA positivity in 9/11 cases. The ALK1-positive cases occured in younger patients (mean age 24.5 years) than the T/null ALK1-negative cases (mean age 50.3 years) or B-cell cases (mean age 51.1 years). Extra-nodal involvement was not significantly more frequent in the ALK1-positive patients. Survival data on 45 patients showed a trend towards longer survival in the patients with the ALK1-positive tumours. The usefulness of ALK1 immunostaining in the diagnosis of anaplastic large cell lymphoma is confirmed. ALK1 positivity defines a distinctive clinicopathologic subgroup of anaplastic lymphoma characterised by T/null phenotype, young age and a relatively good prognosis.