1. ¹Institute of Pathology, Medical University of Innsbruck, Austria
2. ²Institute of Pathology, University of Basel, Switzerland
3. ³Institute of Pathology, Triemli Hospital, Zurich, Switzerland
4. ⁴Chair of Pathologic Anatomy & Lymphoma Unit, Institute of Hematology and Clinical Oncology 'L. & A. Seràgnoli', University of Bologna, Italy
5. ⁵Institute of Pathophysiology, Medical University of Innsbruck, Austria

Correspondence: Dr S Dirnhofer, MD, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4031 Basel, Switzerland. E-mail: sdirnhofer@uhbs.ch

Received 5 May 2004; Revised 9 August 2004; Accepted 10 August 2004; Published online 24 September 2004.

Abstract

The characteristic Hodgkin and Reed–Sternberg cells of classical Hodgkin's lymphoma, although highly positive for proliferation markers, do not accumulate to excessive cell numbers. These cells are characterized by abortive mitotic cycles, leading to multinucleation or cell death in mitosis. We have previously described high expression of G₁-phase cyclins in classical Hodgkin's lymphoma, which could explain the high percentage of cells staining for proliferation markers. To further our understanding of proliferation control in classical Hodgkin's lymphoma, we extended our immunohistochemical analysis to the main S-phase cyclin, cyclin A, and its regulators p21^CIP1 and p27^KIP1. Expression of proliferating cell nuclear antigen (PCNA) was used as an additional marker for cells being in either S- or G₂-phase. In 47% (112/239) of classical Hodgkin's lymphoma cases p21^CIP1 was detected within a mean frequency of 15% positive Hodgkin's and Reed–Sternberg cells per case. Similarly, 47% (116/249) of the cases stained positively for p27^KIP1 with a mean frequency of expression in Hodgkin's and Reed–Sternberg cells of 12%. In contrast, 90% of the cells in all 246 evaluable classical Hodgkin's lymphoma cases were positive for PCNA. In addition, 98% of Hodgkin's and Reed–Sternberg cells in 99% (250/253) of the cases stained strongly positive for cyclin A. These findings further corroborate the hypothesis that Hodgkin and Reed–Sternberg cells exhibit a disturbed cell cycle with an abnormally short or even absent G₁-phase. In contrast to other tumors, expression of PCNA or cyclin A had no prognostic value for patient survival.