High Expression of Minichromosome Maintenance Protein 6 in Classic Hodgkinʹs Lymphoma Points to a Cell Cycle Arrest in G1 Phase

Background: Minichromosome maintenance protein 6 (MCM6) is one of the six proteins of minichromosome maintenance family that are involved in the initiation of DNA replication and thus represent a marker for proliferating cells. The aim of this study was to determine the proliferation characteristics of neoplastic cells in patients with classic Hodgkinʹs lymphoma. Methods: Paraffin-embedded blocks of lymph node, mediastinal, subcutaneous chest wall, and lung mass biopsies of 55 patients with classic Hodgkinʹs lymphoma were immunostained by the proliferation-associated monoclonal antibodies; Ki-S5 (Ki-67 antigen) and Ki-MCM6 (MCM6 antigen). Results: High MCM6 antigen expression was a striking feature of Hodgkinʹs and Reed- Sternberg cells (median: 85%, range: 35 – 99%) in comparison with lower Ki-67 expression (median: 63.5%, range: 1 – 98%, P<0.001). This indicates that MCM6 is already expressed in the early G1 phase, a cell cycle fraction that is not covered by antibodies specific to the Ki-67 antigen. The proliferation rates were determined by two markers, independent of histologic subtype, stage, presence of B symptoms, and size. Conclusion: These data show that a subset of Reed-Sternberg and Hodgkin’s cells is arrested in the early G1 phase and the MCM6-positive cells do not necessarily represent the real proliferating compartment of Hodgkinʹs lymphoma. Clinical relevance of this marker in patients with Hodgkinʹs lymphoma should be investigated.