title: Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine and Hematology, University Hospital of Schleswig-Holstein, Campus Kiel, Chemnitzstr. 33, 24116 Kiel, Germany. c.schrader@med2.uni-kiel.de
authors.forename: C
authors.initials: C
authors.lastname: Schrader
authors.forename: D
authors.initials: D
authors.lastname: Janssen
authors.forename: W
authors.initials: W
authors.lastname: Klapper
authors.forename: J-U
authors.initials: JU
authors.lastname: Siebmann
authors.forename: P
authors.initials: P
authors.lastname: Meusers
authors.forename: G
authors.initials: G
authors.lastname: Brittinger
authors.forename: M
authors.initials: M
authors.lastname: Kneba
authors.forename: M
authors.initials: M
authors.lastname: Tiemann
authors.forename: R
authors.initials: R
authors.lastname: Parwaresch
mesh_terms: D001706:Biopsy; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064151:Minichromosome Maintenance Complex Component 6; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; C103258:MCM6 protein, human; D064151:Minichromosome Maintenance Complex Component 6