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01-01-2013 | Preclinical Study

Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer

Authors: Karin Milde-Langosch, Thomas Karn, Volkmar Müller, Isabell Witzel, Achim Rody, Markus Schmidt, Ralph M. Wirtz

Published in: Breast Cancer Research and Treatment | Issue 1/2013

Abstract

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.

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Title: Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer
Authors: Karin Milde-Langosch
Thomas Karn
Volkmar Müller
Isabell Witzel
Achim Rody
Markus Schmidt
Ralph M. Wirtz
Publication date: 01-01-2013
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2296-x

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