Expression of cyclin D1 protein in centrocytic/mantle cell lymphomas with and without rearrangement of the BCL1/Cyclin D1 gene

Abstract

Centrocytic/mantle cell lymphoma (CC/MCL) is a morphologically defined B-cell non-Hodgkin's lymphoma characterized by a distinctive immunophenotype, BCL1/cyclin Dl (PRAD1) gene rearrangements, and, most recently, by overexpression of cyclin Dl. Even using multiple breakpoint probes for BCL1 (MTC, p94PS) and cyclin Dl, however, only approximately 70% of CC/MCL have a rearrangement consistent with a t(11;14) (q13;q32). To determine whether the type of molecular translocation affects the degree of cyclin Dl expression and to evaluate lymphomas diagnosed as CC/ MCL but lacking molecular evidence of a BCL1 or cyclin D1 translocation, 16 CC/MCL and four cases of small lymphocytic lymphoma/ B-CL1 (SLL/B-CLL) were stained using an anti-cyclin Dl antibody. All cases with a cyclin Dl translocation detected by Southern blotting techniques as well as four of the five CC/MCL without a documentable translocation showed nuclear cyclin Dl protein expression. There was no apparent correlation between staining intensity and the precise site or presence of a detectable translocation. Cases with a mantle zone growth pattern showed infiltration of the cyclin D1 positive cells into reactive follicular centers. None of the four SLL/B-CLL showed cyclin Dl expression. These findings show overexpression of the cyclin Dl protein in virtually all CC/MCL independent of the type or presence of a documentable BCL1 or cyclin Dl molecular rearrangement. The mechanism for cyclin D1 overexpression in the cases without a documentable rearrangement and the relationship of cyclin Dl overexpression to the pathogenesis of mantle cell neoplasia remain uncertain.