Purpose: To test the hypothesis that prognostic information in breast cancer may be derived from an accurate assessment of epithelial cell cycle entry, as indicated by expression of minichromosome maintenance (MCM) proteins.
Materials And Methods: We used immunohistochemistry to examine the distribution of Mcm-2 in breast tissue. Power calculations based on a pilot study of 67 whole tissue sections led to selection of an independent 347-core breast carcinoma tissue microarray validation set. We tested for associations between Mcm-2 (and Ki-67) labeling index (LI) and various clinicopathologic parameters.
Results: Mcm-2 was expressed more frequently than the standard proliferation marker Ki-67 in whole tissue sections of normal breast (P =.0003) and breast carcinoma (P <.0001). In 221 assessable cores of invasive carcinoma, the Mcm-2 LI showed a positive association with tumor size (P =.002), mitotic index (P <.0001), histologic grade (P <.0001), and the Nottingham Prognostic Index (NPI) score (P <.0001). Using a cutoff value of 50%, Mcm-2 LI was associated with overall survival (P =.0007), disease-free interval (P =.0002), and with the development of regional recurrence (P =.011) and distant metastases (P =.0016). Cox regression analysis suggested that the Mcm-2 LI is a strong prognostic factor in breast cancer that is independent and superior to histologic grade, lymph node stage, and Ki-67 LI, but not the NPI score.
Conclusion: Mcm-2 may be of utility as a prognostic marker to refine the prediction of outcome in breast cancer, for example when combined with parameters currently used in the NPI.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1200/JCO.2003.04.121 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alterations in the proteomes of HepG2 and IHKE cells inflicted by six selected mycotoxins.
Arch Toxicol
December 2024
Institute of Food Chemistry, University of Münster, Corrensstraße 45, 48149, Münster, Germany.
Toxic fungal secondary metabolites, referred to as mycotoxins, emerge in moldy food and feed and constitute a potent but often underestimated health threat for humans and animals. They are structurally diverse and can cause diseases after dietary intake even in low concentrations. To elucidate cellular responses and identify cellular targets of mycotoxins, a bottom-up proteomics approach was used.
View Article and Find Full Text PDFStabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.
Nat Commun
December 2024
Department of Biology, Tufts University, Medford, MA, 02155, USA.
Trinucleotide repeats, including Friedreich's ataxia (GAA) repeats, become pathogenic upon expansions during DNA replication and repair. Here, we show that deficiency of the essential replisome component Mcm10 dramatically elevates (GAA) repeat instability in a budding yeast model by loss of proper CMG helicase interaction. Supporting this conclusion, live-cell microscopy experiments reveal increased replication fork stalling at the repeat in mcm10-1 cells.
View Article and Find Full Text PDFInvestigation of an MCM8 gene variant in women with premature ovarian insufficiency.
Einstein (Sao Paulo)
November 2024
Centro Universitário FMABC, Santo André, SP, Brazil.
Article Synopsis
- - The MCM8 gene is crucial for repairing DNA breaks and maintaining cell health, and its dysfunction can lead to cell death, especially in relation to primary ovarian insufficiency.
- - The study aimed to evaluate a specific variant of the MCM8 gene (NG_042869.1:g.40270G>A) in women with primary ovarian insufficiency by comparing samples from affected individuals to those from a control group.
- - Results showed the variant was present in one sample from the case group but absent in the control group, indicating it may be a rare, pathogenic variant associated with primary ovarian insufficiency in the studied population.
MCM double hexamer loading visualized with human proteins.
Nature
December 2024
Macromolecular Machines Laboratory, The Francis Crick Institute, London, UK.
Eukaryotic DNA replication begins with the loading of the MCM replicative DNA helicase as a head-to-head double hexamer at origins of DNA replication. Our current understanding of how the double hexamer is assembled by the origin recognition complex (ORC), CDC6 and CDT1 comes mostly from budding yeast. Here we characterize human double hexamer (hDH) loading using biochemical reconstitution and cryo-electron microscopy with purified proteins.
View Article and Find Full Text PDFMultiple mechanisms for licensing human replication origins.
Nature
December 2024
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Article Synopsis
- The loading of MCM2-7 helicases is crucial for assembling DNA replication machinery, with human loading pathways differing from that of yeast, particularly regarding the role of ORC6.
- Through biochemical reconstitution and electron microscopy, researchers identified several intermediate states in the formation of MCM double hexamers, revealing that ORC6 enhances but is not essential for loading MCM onto DNA.
- The flexibility in the human loading process, including the potential dimerization of independently loaded MCM hexamers, may offer advantages during cellular replication stress, paving the way for future studies on DNA replication initiation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!