© 1997 Kluwer Academic Publishers. Primed in the Netherlands. Original article /?t7-l/eyclin Dl in malignant lymphoma

Mantle-cell lymphoma comprises 2%-10 % of all non-Hodgkin's lymphomas (NHLs). Patients present with generalized disease, and have a poor prognosis. Three different histologic patterns (mantle zone, nodular, and diffuse) and three different cyto-logical variants (classical, blastic, and pleomorphic) have been described. The phenotype (strong surface IgM, CD5+, CD10-, CD23-, cyclin D1+ and B-cell markers+) is remarkably con-stant. Dependent on the methods used (PCR, Southern blot analysis, and cytogenetics) a t(ll;14) can be detected in approx-imately 35%—66 % of cases. Using FISH analysis, possibly almost all cyclin Dl-expressing MCLs carry this translocation, indicat-ing that a substantial part of these translocations are missed by conventional methods. This has been confirmed by DNA fiber FISH analysis by which the breakpoints could be accurately mapped over a 220 kb region centromeric of the cyclin Dl gene. Additional genetic abnormalities involve breakpoints and dele-tion at the 3 ' end of the cyclin Dl gene, numerical chromosomal aberrations, mutations in p53, and deletions of pl6. These may be associated with tumor progression. Owing to the transloca-tion t(ll;14), the cyclin Dl gene is activated. At the RNA level, approximately 90 % of MCLs show overexpression. This cor-roborates immunohistochemistry on paraffin tissue sections. Since expression of cyclin Dl in normal lymphoid cells is very low to undetectable, and only hairy-cell leukemia and very few other B-cell lymphomas show expression, immunohistochemis-try for cyclin Dl provides an excellent marker for MCL. In hairy-cell leukemia, expression is moderate and cannot be explained by chromosomal translocation