Repp86: a new prognostic marker in mantle cell lymphoma

Schrader, Carsten; Janssen, Dirk; Meusers, P.; Brittinger, G.; Siebmann, Jens U.; Parwaresch, Reza; Tiemann, Markus

doi:10.1111/j.1600-0609.2005.00540.x

Cited by 18 publications

(11 citation statements)

References 24 publications

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“…These data are in line with our results of repp86 in a large series of 94 patients with MCL (Schrader et al, 2005). Repp86 is a spindle apparatusassociated protein expressed only during S/G2/M, absent in G1 and G0, and thus displaying the same cell cycle expression pattern like geminin (Heidebrecht et al, 1997(Heidebrecht et al, , 2003Lygerou and Nurse, 2000;Wohlschlegel et al, 2000;Madine and Laskey, 2001;Hodgson et al, 2002).…”

Section: Discussionsupporting

confidence: 86%

“…As this cell cycle arrest has been shown by others Eward et al, 2004;Obermann et al, 2005;Tachibana et al, 2005), we could demonstrate that this has a clinical relevance in patients with MCLs. Our data on expression of repp86 in MCL (Schrader et al, 2005) showed that real proliferation activity is an important prognostic factor in MCL. On the other hand, patients with cell arrest (G1 arrest) indicated by high MCM6 expression also predict survival in this disease.…”

Section: Discussionmentioning

confidence: 61%

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

et al. 2005

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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 (Po0.0001). 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, Po0.0001). 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.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 61%

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

et al. 2005

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“…Actually, based on the recent European MCL Network's clinicopathological study of 304 cases of MCLs, the cell proliferation was identified as a strong prognosticator [7]. In addition, multivariate analyses exposed the immunohistochemically assessed Ki-67, topoisomerase IIα, and TPX2 level as the most effective prognostic factor in MCL patients, even superior to the International Prognostic Index and other clinical and histomorphological characteristics [6,14,15]. The predictive role of KI-67 was also confirmed for MCL patients treated with anti-CD20 therapy, and it was reported as an important biological marker also in addition to MCL International Prognostic Index [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…The predictive role of various clinical and laboratory parameters in the MCL progression is conflicting [6][7][8][9][10][11][12][13][14][15]. Actually, based on the recent European MCL Network's clinicopathological study of 304 cases of MCLs, the cell proliferation was identified as a strong prognosticator [7].…”

Section: Introductionmentioning

confidence: 99%

A novel quantitative PCR of proliferation markers (Ki-67, topoisomerase IIα, and TPX2): an immunohistochemical correlation, testing, and optimizing for mantle cell lymphoma

et al. 2010

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A clinical course of patients with mantle cell lymphoma (MCL) is aggressive, and the disease is rarely curable. Proliferation rate is the most important prognostic factor. We developed a novel, reliable, rapid, and routinely applicable approach allowing a precise quantitative assessment of three proliferation markers, Ki-67, topoisomerase IIalpha, and TPX2. A total of 95 lymphoma specimens were measured in the study by real-time reverse transcription PCR (RQ-RT-PCR). We tested the reproducibility and accuracy of the assay and correlated the results with the immunohistochemical staining of the corresponding proteins. The results obtained indicated individual variability of the mRNA expression levels, reflecting heterogeneity of the proliferation rate in individual patients. In general, we observed the highest mRNA expression in the group of Burkitt lymphomas and the lowest in patients with reactive lymphadenopathies. We found increased proliferation rate in MCLs with high cyclin D1 mRNA, indicating a quantitative control of the cell cycle. We observed a correlation between mRNA expression level and the immunohistochemical staining of corresponding proteins, which significantly argues for the prognostic significance of the mRNA expression measuring. We confirmed the accuracy of the current assay for a precise quantitative examination of the proliferation activity. Real-time RT-PCR provides a novel approach applicable for clinical trials, and it represents a potent approach allowing to stratify MCL patients for entry into clinical trials according to the expression of the proliferation signature genes in their tumors. This approach may contribute to improved and individualized therapeutic options respecting the individual progression risk of patients with MCL.

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“…45,46). Proliferation markers studied in MCL include Ki-67, topoisomerase IIa, MDM2, repp86, and survivin (47)(48)(49)(50)(51). However, except for Ki-67, none of these biomarkers have to date been validated in larger cohorts (Table 1).…”

Section: Ki-67 Index and Other Immunohistochemically Assessed Prolifementioning

confidence: 99%

New Paradigms in Mantle Cell Lymphoma: Is It Time to Risk-Stratify Treatment Based on the Proliferative Signature?

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Vogt

et al. 2014

Clinical Cancer Research

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The elucidation of crucial biologic pathways of cell survival and proliferation has led to the development of highly effective drugs, some of which have markedly improved mantle cell lymphoma (MCL) therapeutic opportunities in the past 10 years. Moreover, an undeniable clinical heterogeneity in treatment response and disease behavior has become apparent in this neoplasm. Thus, the need for biologic markers stratifying patients with MCL in risk classes deserving different treatment approaches has recently been fervently expressed. Among several newly discovered biomarkers, the dismal predictive value of a high proliferative signature has been broadly recognized in large studies of patients with MCL. Different techniques have been used to assess tumor cell proliferation, including mitotic index, immunostaining with Ki-67 antibody, and gene expression profiling. Ki-67 proliferative index, in particular, has been extensively investigated, and its negative impact on relapse incidence and overall survival has been validated in large prospective clinical trials. However, one important pitfall limiting its widespread use in clinical practice is the reported interobserver variability, due to the previous lack of a standardized approach for quantification among different laboratories. In the present review, we describe some of the major techniques to assess cell proliferation in MCL, focusing in particular on the Ki-67 index and its need for a standardized approach to be used in multicenter clinical trials. The value of MCL biologic prognostic scores (as MIPI-b) is discussed, along with our proposal on how to integrate these scores in the planning of future trials investigating a tailored therapeutic approach for patients with MCL.

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Repp86: a new prognostic marker in mantle cell lymphoma

Abstract: Based on these findings, repp86 expression is a new important prognostic factor in MCL.

Cited by 18 publications

References 24 publications

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

A novel quantitative PCR of proliferation markers (Ki-67, topoisomerase IIα, and TPX2): an immunohistochemical correlation, testing, and optimizing for mantle cell lymphoma

New Paradigms in Mantle Cell Lymphoma: Is It Time to Risk-Stratify Treatment Based on the Proliferative Signature?

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