Source:http://linkedlifedata.com/resource/pubmed/id/18620730
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2008-9-8
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pubmed:abstractText |
Gene expression studies have identified a basal phenotype of breast cancer; these are hormone receptor and HER2-negative cancers with poor prognosis. High levels of cyclin E and Skp2, and low levels of p27 have previously been individually associated with both basal-like breast cancer and a poor outcome after diagnosis. The goal of this study was to first confirm the prognostic value of these biomolecular markers using a breast cancer tissue microarray. Second, we also test the hypothesis that the combined phenotype of high cyclin E, low p27, and high Skp2 would be a strong predictor of outcome and would be closely associated with the basal phenotype of breast cancer. Our cohort consisted of 438 cases of breast cancer and the median follow-up was 15.4 years. The tissue microarray was constructed from archival tumor blocks and we used commercially available antibodies for biomarker immunostaining. Cyclin E was positive in 46% of cases, p27 was negative in 62%, and Skp2 was positive in 35%. We found cyclin E and Skp2 to be prognostic for breast cancer-specific survival in univariate analyses, but p27 was not prognostic. The strongest predictor of outcome was the combination of cyclin E positive and Skp2 positive (difference in survival of 19% at 10 years, P = .0009). This combination was present in 78 (27%) of 288 cases for which data on both biomarkers were available. This combination was also highly associated with young age at diagnosis, grade 3 tumors, ER-negative status, HER2-negative status, and the basal biomarkers epidermal growth factor receptor and cytokeratin 5/6. However, in a multivariate model including standard clinicopathologic variables, this combination was not found to have independent prognostic significance. In conclusion, the combination of high cyclin E and Skp2 expression predicts for poor prognosis in breast cancer in univariate analysis only, it is associated with high risk features, and it is associated with the basal phenotype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin E,
http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/S-Phase Kinase-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/p27 antigen
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1532-8392
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1431-7
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pubmed:meshHeading |
pubmed-meshheading:18620730-Breast Neoplasms,
pubmed-meshheading:18620730-Cell Nucleus,
pubmed-meshheading:18620730-Cyclin E,
pubmed-meshheading:18620730-Female,
pubmed-meshheading:18620730-Humans,
pubmed-meshheading:18620730-Lymph Nodes,
pubmed-meshheading:18620730-Lymphatic Metastasis,
pubmed-meshheading:18620730-Middle Aged,
pubmed-meshheading:18620730-Phenotype,
pubmed-meshheading:18620730-Prognosis,
pubmed-meshheading:18620730-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:18620730-S-Phase Kinase-Associated Proteins,
pubmed-meshheading:18620730-Survival Rate,
pubmed-meshheading:18620730-Tissue Array Analysis,
pubmed-meshheading:18620730-Tumor Markers, Biological
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pubmed:year |
2008
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pubmed:articleTitle |
The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype.
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pubmed:affiliation |
Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6. dvoduc@bccancer.bc.ca
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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