High expression of minichromosome maintenance protein 6 in classic Hodgkin's 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 Hodgkin's lymphoma. METHODS Paraffin-embedded blocks of lymph node, mediastinal, subcutaneous chest wall, and lung mass biopsies of 55 patients with classic Hodgkin's 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 Hodgkin's 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 Hodgkin's lymphoma. Clinical relevance of this marker in patients with Hodgkin's lymphoma should be investigated.