Expression of Cell Cycle Regulating Proteins in an Unusual Transformation of Mantle Cell Lymphoma

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Abstract
We describe here two patients with mantle cell lymphoma (MCL) who after a few years, developed to the diffuse large cell lymphoma (DLCL)(anaplastic centrocytic lymphoma) growing in a diffuse sheets without the classical MCL component. In both the initial and second biopsy specimens, in each case, tumor cells were positive for cyclin D1, sIgM, sIgD, and CD5, but were negative for CDlO and CD23. In a study of immunoglobulin heavy chain (IgH) gene rearrangement, using the polymerase chain reaction (PCR) method, the products obtained from each paired biopsy tissue sample were the same size, and in one case had an identical sequence to the non-mutated VH gene. Immunohistochemistry was used to examine the expression of p53, p27kipl and cyclin E. Interestingly, there was clear overexpression of p53 protein in case 1 but not in case 2, compared with other typical MCL cases. The expression of p27kipi in the second biopsies of each case was decreased compared with those in the initial biopsies. In case 2, however, p27kipi was clearly expressed in the first and second biopsies, in contrast to other typical MCL cases. Thus these 2 cases demonstrate not only that the variant form of MCL may arise de novo, but also that MCL may transform to DLCL at the time of relapse. Although the mechanism of tumor rogressiodtransforrnation is still poorly understood, the overexpression of p53 or p27kipi may be linked to a cellular mechanism involved in the development of the variant form of MCL.