Clinicopathologic study of malignant lymphoma immunohistochemically showing cyclin D1 protein overexpression with special reference to mantle cell lymphoma

The overexpression of PRAD1/cyclin D1 gene activated by the 11q13 translocation and its molecular counterpart BCL-1 rearrangement is frequently associated with mantle cell lymphomas (MCLs). We recently described that the positive nuclear staining observed with monoclonal antibody against a recombinant PRAD1/cyclin D1 product correlates with the mRNA overexpression in MCLs. In the present study, we have immunohistochemically examined the cyclin D1 protein in a large series of 295 lymphoproliferative diorders including 39 MCLs on paraffin sections. Based on the expression of cyclin D1 protein and CD5, and morphological features of the tumor cells, three groups of MCL-related lesions were identified among the B-cell lymphomas examined; 36 cases with cyclin D1 overexpression, 35 (97%) of which exhibited CD5-positivity and MCL morphology often with naked germinal centers (Group A); 14 cases of CD5-positive lymphoma without cyclin D1, 10 of which showed the histology of diffuse large cell lymphoma with sparing of follicles (Group B); 6 cases of CD5-negative lymphmas without cyclin D1, but which were within the morphological boundaries described of MCL (Group C). The patients with Group A clinicopathologically constituted a very homogeneous group, their ages ranging from 46 to 81 (mean, 64 years of age), and the 5-year survival rate being 19%. Although several differences were noted in the histologic, phenotypic and genotypic pictures of each group, there was no significant difference in the clinical pictures among the three groups, and the patients with Group A and B had the similar survival curves. The BCL-2 protein was expressed in all cases of three groups, while most of the cases lacked p53 protein. These three groups sometimes overlapped their histologic and phenotypic spectrums, and it was difficult to distinguish one from the other on several occasions. We therefore propose that the immunolocalization of cyclin D1 protein is an essential marker for the definite diagnosis of MCL.