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Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer.
MedLine Citation:
PMID:  23135572     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
High proliferation rates are characteristic of cancer, and proliferation markers make up the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. Based on prior data on differences in molecular subgroups of breast cancer, we hypothesized that the significance of single proliferation markers might differ in luminal, Her2-positive and triple-negative subtypes. Therefore, we compared mRNA expression data of Ki67, TOP2A, and RacGAP1 using a pool of 562 Affymetrix U133A microarrays from breast cancer samples. "Luminal," "triple-negative," and "Her2-positive" subcohorts were defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs. The analysis of the three potential proliferation markers revealed subtype-specific differences: in luminal carcinomas, expression of all three markers was a significant indictor of early recurrence in univariate and multivariate analysis, but RacGAP1 was superior to Ki67 and TOP2A in significance. In triple-negative tumors, only Ki67 was a significant and independent marker, whereas none of the markers showed a significant prognostic impact in Her2-positive cases. Within the group of luminal carcinomas, the proliferation markers had different impact depending on the treatment of patients: in untreated patients, Ki67, TOP2A, and RacGAP1 were significant and independent prognostic markers. In chemotherapy-treated patients, overexpression of all three markers was predictive for early recurrence, but only RacGAP1 retained significance in multivariate analysis. In contrast, RacGAP1 was the only predictive proliferation marker in the endocrine treatment group. These data point to subtype-specific differences in the relevance of proliferation-associated genes, and RacGAP1 might be a strong prognostic and predictive marker in the luminal subgroup.
Authors:
Karin Milde-Langosch; Thomas Karn; Volkmar Müller; Isabell Witzel; Achim Rody; Markus Schmidt; Ralph M Wirtz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  -     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Gynecology, University Hospital Hamburg-Eppendorf, Hamburg, Germany, milde@uke.de.
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