Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma - A distinct molecular pathologic entity

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression or PRAD1/cyclin D1, activated by 11q13 translocation and iis molecular counterpart rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. in the present study, we immunohistochemically Investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders. including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity. CD expression; and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group I) four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II). four cases of lymphomas without cyclin D1 overexpression and surface: CD5 but that fall within the morphologic boundaries or MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated guile homogeneous clinicopathologic feature identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis fur further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.