bcl‐1 REARRANGEMENT AND CYCLIN D1 PROTEIN EXPRESSION IN MANTLE CELL LYMPHOMA

Abstract

Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1-S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas (n = 40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL.

The value of immunohistochemistry on paraffin wax embedded tissue sections in the differentiation of small lymphocytic and mantle cell lymphomas.

“…Mantle cell lymphoma is characterised by a translocation between the Cyclin DI gene on chromosome 11 and the immunoglobulin heavy chain gene on chromosome 1422-25 in about 70% of cases.26 This translocation results in the overexpression of Cyclin D 1 in the nuclei of the tumour cells of MCL,27 which is also seen in cases of MCL without detectable molecular evidence of t (1 1;14).26 27 With one exception, expression of Cyclin D1 has not been seen in B-SLL. It has also been recorded rarely in hairy cell leukaemia and plasmacytoma.25 Our studies confirm Cyclin D1 as the most reliable marker for the distinction between B-SLL and MCL.…”

Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma

“…2 3 Interest in a possible role of cyclin D1 in tumorigenesis has grown since experiments demonstrated that induction of cyclin D1 in cells arrested in the early G1 phase by transfection with pRB was sufficient for cell cycle completion 4. Further, cyclin D1 overexpression has been reported in several tumours including parathyroid adenomas,5 mantle cell lymphoma,6 7malignant melanoma of the skin,8 as well as carcinomas of the breast, lung, liver, oesophagus, urinary bladder, head and neck, vulva, and uterine cervix 8-14…”

Morphologic diagnosis of leukaemic B-lymphoproliferative disorders and the role of cyclin D1 expression

“…The immunohistochemical detection of overexpression of cyclin D1 is important for the histological diagnosis of mantle cell lymphoma in lymph node biopsy (Yang et al 1994;de Boer et al 1995;Swerdlow et al 1995Swerdlow et al , 1996Zukerberg et al 1995;Ott et al 1996;Majlis et al 1997;Vasef et al 1997;Aquilera et al 1998). Cyclin D1 protein overexpression is the result of the BCL-1 rearrangement, which is detectable in 70-80% of mantle cell lymphomas (Williams et al 1991).…”

“…The International Lymphoma Study Group included mantle cell lymphoma in the REAL classification . A rearrangement of the bcl-1/cyclin D1 oncogene is usually present (Williams et al 1991) and leads to overexpression of cyclin D1 protein (Yang et al 1994;de Boer et al 1995;Swerdlow et al 1995Swerdlow et al , 1996Zukerberg et al 1995;Ott et al 1996;Majlis et al 1997;Vasef et al 1997;Aquilera et al 1998). We investigated the expression of cyclin D1 protein in 108 patients with leukaemic B-lymphoproliferative disorders and describe its importance for the differentiation of the leukaemic phase of these disorders.…”