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Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer.
Breast Cancer Res Treat. 2013 Jan; 137(1):57-67.BC

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.

Authors+Show Affiliations

Department of Gynecology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. milde@uke.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23135572

Citation

Milde-Langosch, Karin, et al. "Validity of the Proliferation Markers Ki67, TOP2A, and RacGAP1 in Molecular Subgroups of Breast Cancer." Breast Cancer Research and Treatment, vol. 137, no. 1, 2013, pp. 57-67.
Milde-Langosch K, Karn T, Müller V, et al. Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. Breast Cancer Res Treat. 2013;137(1):57-67.
Milde-Langosch, K., Karn, T., Müller, V., Witzel, I., Rody, A., Schmidt, M., & Wirtz, R. M. (2013). Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. Breast Cancer Research and Treatment, 137(1), 57-67. https://doi.org/10.1007/s10549-012-2296-x
Milde-Langosch K, et al. Validity of the Proliferation Markers Ki67, TOP2A, and RacGAP1 in Molecular Subgroups of Breast Cancer. Breast Cancer Res Treat. 2013;137(1):57-67. PubMed PMID: 23135572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. AU - Milde-Langosch,Karin, AU - Karn,Thomas, AU - Müller,Volkmar, AU - Witzel,Isabell, AU - Rody,Achim, AU - Schmidt,Markus, AU - Wirtz,Ralph M, Y1 - 2012/11/08/ PY - 2012/08/31/received PY - 2012/10/11/accepted PY - 2012/11/9/entrez PY - 2012/11/9/pubmed PY - 2013/5/29/medline SP - 57 EP - 67 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 137 IS - 1 N2 - 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. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/23135572/Validity_of_the_proliferation_markers_Ki67_TOP2A_and_RacGAP1_in_molecular_subgroups_of_breast_cancer_ L2 - https://doi.org/10.1007/s10549-012-2296-x DB - PRIME DP - Unbound Medicine ER -