Cytogenetic studies of B-cell neoplasms have shown that some of the reciprocal chromosomal translocations are closely correlated with specific histological and immunological phenotypes. Recently developed molecular genetic techniques have demonstrated that genes which are located at the breakpoints of these nonrandom transloca-tions play an integral role in the development of the lymphoid neoplasms. The t(11; 14) (q13; q32), t(14; 19) (q32; q13) and t(14; 18) (q32; q21), involving the BCL1/PRAD1, BCL3 and BCL2 genes, respectively, are the well characterized examples of translocations observed in B-cell lymphoma and leukemia. The translocations result in the juxtaposition of these proto-oncogenes with the immunoglobulin gene loci leading to deregulation of the genes. In contrast, the 3q27 translocation affecting the BCL6 gene is unique in that the translocation can involve not only immunoglobulin genes but also other unchar-acterized chromosomal loci. This study summarizes data with regard to incidence of these oncogene rearrangements in Japanese B-cell neoplasms and describes characteristic clinicopathological features of patients associated with particular genetic abnormalities. Finally, we refer briefly to implications of p53 mutations in the development and progression of B-cell neoplasms.

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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.

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We developed an improved technique that permits simultaneous surface phenotyping and DNA/RNA quantitation by a flow cytofluorometry using FITC-conjugated monoclonal antibodies, 7-amino-actinomycin D and pyronin Y, respectively. Clinical samples from patients with non-Hodgkin's lymphoma were analyzed for cell cycle using 7AAD/PY. Pathological lymphoma cells and reactive normal lymphocytes from clinical samples were separately analyzed for ploidy, cell growth and light scattering profiles. The effect of growth factors on pathological cells was also analyzed using 7AAD/PY in vitro. 7AAD/PY may be useful for clinical diagnosis of lymphoma, as well as predicting the effectiveness of chemotherapy and the prognosis of disease in a clinical setting and to analyze in the vitro effects of biological effectors such as chemotherapy drugs, growth factors and other biological modifying factors.

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Positorn emission tomgraphy (PET) has been used and studied in patients with various kinds of neoplasms in a few decades. We have studied PET using Fluorine-18-fluorodeoxyglucose (FDG) in malignant lymphoma. and some findings have been dis-coverd. FDG uptake of lymphoma closely revealed the glucose metabolic rate. The uptake was higher than normal soft tissue. Especially, high-grade or aggressive lymphoma likely showed higher FDG uptake. FDG-PET may be useful for tumor-seeking, grading and predicting the prognosis in lymphoma.

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