Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL

Therapie der Non-Hodgkin-Lymphome (NHL) von hohem Malignitaetsgrad des Erwachsenenalters Schlussbericht

With the aim to improve the induction polychemotherapy in stage II-IV (Ann Arbor classification) high grade malignant non-Hodgkin lymphoma, the sequential application of two regimens was evaluated (COP-BLAM/IMVP-16 protocol). According to the results of an early restaging evaluation, the switch to the second regimen was performed response-adapted after 3 (in case of partial remission) or 5 (in case of complete remission) cycles of COP-BLAM/IMVP-16. After completion of chemotherapy, patients in complete remission were randomized to receive additional radiotherapy or remain without further treatment. 593 patients were recruited in a multicenter trial, median observation time 55 months. The rate of complete remissions was 60% and the relapse-free and overall survival 57% and 52% after 4 years. There was no prognostic difference between patients randomized to radiotherapy and those followed without. Instead, detailed analyses of prognostic risk revealed that the long-term prognosis was predominantly influenced by the presence of crucial initial parameters. In younger patients with lymphoblastic lymphoma a multiphase regimen was evaluated and a 4-years survival of 44% was achieved. (orig.)SIGLEAvailable from TIB Hannover: F94B0422 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman