Expression of cyclin D1 protein in centrocytic/mantle cell lymphomas with and without rearrangement of the BCL1/cyclin D1 gene.
Centrocytic/mantle cell lymphoma (CC/MCL) is a morphologically defined B-cell non-Hodgkin's lymphoma characterized by a distinctive immunophenotype, BCL1/cyclin D1 (PRAD1) gene rearrangements, and, most recently, by overexpression of cyclin D1. Even using multiple breakpoint probes for BCL1 (MTC, p94PS) and cyclin D1, 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 D1 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 D1 antibody. All cases with a cyclin D1 translocation detected by Southern blotting techniques as well as four of the five CC/MCL without a documentable translocation showed nuclear cyclin D1 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 D1 expression. These findings show overexpression of the cyclin D1 protein in virtually all CC/MCL independent of the type or presence of a documentable BCL1 or cyclin D1 molecular rearrangement. The mechanism for cyclin D1 overexpression in the cases without a documentable rearrangement and the relationship of cyclin D1 overexpression to the pathogenesis of mantle cell neoplasia remain uncertain.
Swerdlow
S H
SH
Department of Pathology, University of Pittsburgh School of Medicine, PA, USA.
Yang
W I
WI
Zukerberg
L R
LR
Harris
N L
NL
Arnold
A
A
Williams
M E
ME
D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism*; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D013194:Staining and Labeling
D016213:Cyclins; D015513:Oncogene Proteins; D019938:Cyclin D1