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Cited by 21Breast Cancer Treatment StudiesBreast Lesions and CarcinomasGastric Cancer Management and Outcomes

The potential utility of geminin as a predictive biomarker in breast cancer.

Sundara Rajan, Sreekumar, Hanby, Andrew M., Horgan, Kieran, Thygesen, Helene H., Speirs, Valerie·2014·Breast Cancer Research and Treatment
DOI 10.1007/s10549-013-2786-5
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Abstract

Compared with other markers of cell proliferation, geminin is unique being expressed selectively during the proliferative phase of the cell cycle, specifically S, G2 and early mitosis, disappearing completely at the metaphase-anaphase transition. We aimed to compare the prognostic significance of geminin to that of Ki67, a proliferation marker which has been investigated in many breast cancer studies. Breast cancer tissue microarrays containing 368 tumours were stained using anti-geminin and Ki67 antibodies. Labelling index (LI) was calculated for geminin, and the percentage of positive cancer nuclei was determined for Ki67. A receiver operation characteristics analysis was used to determine the optimum cut-off value for geminin (LI ≥ 2), and for Ki67, a score of ≥14 % was considered as positive for survival analysis. Geminin expression correlated positively with Ki67 expression (r = 0.686, p = 0.001). Survival analysis showed only geminin, and not Ki67-positive patients to have poor (breast cancer-specific survival) BCSS [HR 2.85 (1.53-5.32)] and (disease-free survival) DFS [HR 2.63 (1.47-4.71)]. On univariate analysis, along with known clinicopathological variables, both Ki67 and geminin LI were found to be significant predictors of BCSS and DFS. On multivariate analysis, only tumour size, nodal status and adjuvant hormonal therapy were found to be independent predictors for both BCSS and DFS, while geminin positivity (LI ≥ 2 %) was found to be an independent predictor for BCSS [HR 2.27 (1.01-5.06); p = 0.04]. In comparison with Ki67, a more established proliferation marker, geminin expression was a better predictor of adverse outcome in this cohort of breast cancers. Selective expression of geminin during the proliferative phase of the cell cycle and its nuclear specificity increase its potential to be used as an alternative marker of proliferation in breast cancer patients.

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  • High Geminin protein levels are prognostic of poor clinical outcome and are associated with genome instability, DNA replication errors and aneuploidy.

    “High Geminin protein levels are prognostic of poor clinical outcome and are associated with genome instability, DNA replication errors and aneuploidy (Sundara Rajan et al., 2014).”

    From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Sundara Rajan et al., 2014

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Authors
Sundara Rajan, S., Hanby, A. M., Horgan, K., Thygesen, H. H., & Speirs, V.
Affiliations
  • University of Leeds (GB)
  • Leeds Teaching Hospitals NHS Trust (GB)
Corresponding author
Speirs, Valerie
ORCID
Venue
Breast Cancer Research and Treatment
Publisher
Springer Science and Business Media LLC
Published
2013-12-01
Volume
143
Issue
1
Pages
91-98
ISSN
  • 0167-6806 (ISSN-L)
  • 1573-7217
DOI
10.1007/s10549-013-2786-5
OpenAlex
W2081231955
Cited by
21
References
32
Citations by year
2023: 1 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 2
FWCI
0.70
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Breast Cancer Research and Treatment (publishedVersion)
  • PubMed (publishedVersion)
Funders
Cancer Research UK
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
Keywords
geminin, Ki-67, breast cancer, predictive biomarkers, cell proliferation markers, cell cycle, breast cancer-specific survival, disease-free survival, prognostic factors, labeling index
MeSH terms
Adult, Aged, Aged, 80 and over, Breast Neoplasms, Female, Humans, Immunohistochemistry, Middle Aged, Neoplasm Metastasis, Prognosis, Risk Factors, ROC Curve, Cohort Studies, Biomarkers, Ki-67 Antigen, Neoplasm Grading, Geminin

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