Cyclin D1 and E2F-1 immunoreactivity in bone marrow biopsy specimens of multiple myeloma: relationship to proliferative activity, cytogenetic abnormalities and DNA ploidy

Cyclin D1, encoded by the CCND1 gene, is immunohistochemically detectable i n up to one-third of cases of multiple myeloma (MM). To examine the mechani sm of cyclin D1 overexpression, we compared cyclin D1 immunoreactivity with the results of conventional cytogenetics to determine if the t(11;14)(q13; q32) or other abnormalities of 11q11-14 explained cyclin D1 overexpression. Karyotypic abnormalities were found in 45 out of 67 (67%) MM cases: the t( 11;14) was present in seven cases (10%). Additional 11q11-14 abnormalities were not identified. The t(11;14) correlated with cyclin D1 upregulation in low to intermediately proliferative MM, but was not present in highly prol iferative tumours (assessed using bromodeoxyuridine labelling index). Cycli n D1 indirectly activates the transcription factor E2F-1. In the bone marro w biopsy specimens of MM cases, E2F-1 was concurrently expressed with cycli n D1 (P = 0.001), indicating that cyclin D1 is functional. However, as neit her E2F-1 nor cyclin D1 expression correlated with proliferative activity, the speculation that t(11;14) upregulates the CCND1 gene to induce higher p roliferation end possibly more aggressive disease is not supported, We conc lude that in low to intermediately proliferative MM cases, cyclin D1 is pro bably upregulated by t(11;14), but an alternative mechanism is more probabl e in highly proliferative MM.