1. ¹Department of Pathology, Medical Faculty, University of Ioannina, Ioannina
2. ²Department of Pathology, Agia Sophia Hospital, Athens
3. ³Department of Pathology, Evangelismos Hospital, Athens
4. ⁴Department of Anatomy-Histology-Embryology, Medical Faculty, University of Ioannina, Ioannina, Greece

Correspondence: Dr M Bai, MD, PhD, Department of Pathology, Medical School, University of Ioannina 45110, Ioannina, Greece. E-mail: mbai@cc.uoi.gr

Received 26 February 2004; Revised 26 April 2004; Accepted 26 April 2004; Published online 3 September 2004.

Abstract

There is accumulating evidence that Hodgkin's and Reed–Sternberg cells of classical Hodgkin's lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkin's and Reed–Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkin's and Reed–Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkin's and Reed–Sternberg cells.