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Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma
CJ de Boer, E Schuuring, E Dreef, G Peters, J Bartek, PM Kluin and JH van Krieken
Department of Pathology, University of Leiden, The Netherlands.
Mantle cell lymphoma (MCL) is a clinicopathologic entity that is difficult
to diagnose on histopathologic criteria. Approximately 50% to 70% of MCL
contain a t(11;14)(q13;q32) translocation involving the cyclin D1 gene.
Irrespective of this rearrangement, almost all MCL show overexpression of
the cyclin D1 gene at the mRNA level. Other B-cell non-Hodgkin's lymphomas
(NHL) do not show this rearrangement or overexpression of cyclin D1. We
developed an immunohistochemical assay to detect overexpression of the
cyclin D1 protein on conventional formalin-fixed, paraffin-embedded
biopsies using the well-defined monoclonal antibody DCS-6. Expression in
tumor cells was compared with expression of cyclin D1 in endothelial cells
and fibroblasts. An exclusively nuclear staining pattern was observed.
Moreover, expression was directly compared with the expression observed by
immunoblot analysis with the same antibody, as well as with mRNA expression
and with the occurrence of genomic rearrangements within the BCL-1 locus.
Of 13 MCL that were analyzed by immunohistochemistry and immunoblot, 12
showed overexpression with both techniques, whereas no overexpression was
observed in 39 other NHL. Of 13 additional MCL studied either by
immunohistochemistry or immunoblot, 11 also showed overexpression. Two
lymphomas morphologically indistinguishable from MCL but with an aberrant
immunophenotype (CD5 negative, CD10 positive) both lacked overexpression of
cyclin D1. These results underscore the significance of overexpression of
the cyclin D1 protein as a specific marker for MCL. Detection of cyclin D1
overexpression on formalin-fixed, paraffin- embedded tissues using the
DCS-6 monoclonal antibody can be applied for routine diagnostic purposes.
Volume 86,
Issue 7,
pp. 2715-2723,
10/01/1995
Copyright © 1995 by The American Society of Hematology
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