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

Karin Milde-Langosch; Thomas Karn; Volkmar Müller; Isabell Witzel; Achim Rody; Markus Schmidt; Ralph M Wirtz

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

Standard

Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. / Milde-Langosch, Karin; Karn, Thomas; Müller, Volkmar; Witzel, Isabell; Rody, Achim; Schmidt, Markus; Wirtz, Ralph M.

in: BREAST CANCER RES TR, Jahrgang 137, Nr. 1, 1, 2013, S. 57-67.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Milde-Langosch, K, Karn, T, Müller, V, Witzel, I, Rody, A, Schmidt, M & Wirtz, RM 2013, 'Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer.', BREAST CANCER RES TR, Jg. 137, Nr. 1, 1, S. 57-67. <http://www.ncbi.nlm.nih.gov/pubmed/23135572?dopt=Citation>

APA

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 RES TR, 137(1), 57-67. [1]. http://www.ncbi.nlm.nih.gov/pubmed/23135572?dopt=Citation

Vancouver

Milde-Langosch K, Karn T, Müller V, Witzel I, Rody A, Schmidt M et al. Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. BREAST CANCER RES TR. 2013;137(1):57-67. 1.

Bibtex

@article{4d8b0931c5a14edc89af9dd514cf08cb,

title = "Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer.",

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.",

keywords = "Adult, Humans, Aged, Female, Middle Aged, Aged, 80 and over, Multivariate Analysis, Treatment Outcome, Prognosis, Disease-Free Survival, Proportional Hazards Models, Retrospective Studies, Gene Expression, Cell Proliferation, Kaplan-Meier Estimate, Receptor, erbB-2/metabolism, Tumor Markers, Biological/*genetics/metabolism, DNA-Binding Proteins/*genetics/metabolism, Receptors, Progesterone/metabolism, RNA, Messenger/genetics/metabolism, Receptors, Estrogen/metabolism, Antigens, Neoplasm/*genetics/metabolism, Breast Neoplasms/*metabolism/mortality/pathology/therapy, Carcinoma, Ductal, Breast/*metabolism/mortality/pathology/therapy, Carcinoma, Lobular/*metabolism/mortality/pathology/therapy, DNA Topoisomerases, Type II/*genetics/metabolism, GTPase-Activating Proteins/*genetics/metabolism, Ki-67 Antigen/*genetics/metabolism, Adult, Humans, Aged, Female, Middle Aged, Aged, 80 and over, Multivariate Analysis, Treatment Outcome, Prognosis, Disease-Free Survival, Proportional Hazards Models, Retrospective Studies, Gene Expression, Cell Proliferation, Kaplan-Meier Estimate, Receptor, erbB-2/metabolism, Tumor Markers, Biological/*genetics/metabolism, DNA-Binding Proteins/*genetics/metabolism, Receptors, Progesterone/metabolism, RNA, Messenger/genetics/metabolism, Receptors, Estrogen/metabolism, Antigens, Neoplasm/*genetics/metabolism, Breast Neoplasms/*metabolism/mortality/pathology/therapy, Carcinoma, Ductal, Breast/*metabolism/mortality/pathology/therapy, Carcinoma, Lobular/*metabolism/mortality/pathology/therapy, DNA Topoisomerases, Type II/*genetics/metabolism, GTPase-Activating Proteins/*genetics/metabolism, Ki-67 Antigen/*genetics/metabolism",

author = "Karin Milde-Langosch and Thomas Karn and Volkmar M{\"u}ller and Isabell Witzel and Achim Rody and Markus Schmidt and Wirtz, {Ralph M}",

year = "2013",

language = "English",

volume = "137",

pages = "57--67",

journal = "BREAST CANCER RES TR",

issn = "0167-6806",

publisher = "Springer New York",

number = "1",

}

RIS

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

PY - 2013

Y1 - 2013

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.

AB - 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.

KW - Adult

KW - Humans

KW - Aged

KW - Female

KW - Middle Aged

KW - Aged, 80 and over

KW - Multivariate Analysis

KW - Treatment Outcome

KW - Prognosis

KW - Disease-Free Survival

KW - Proportional Hazards Models

KW - Retrospective Studies

KW - Gene Expression

KW - Cell Proliferation

KW - Kaplan-Meier Estimate

KW - Receptor, erbB-2/metabolism

KW - Tumor Markers, Biological/genetics/metabolism

KW - DNA-Binding Proteins/genetics/metabolism

KW - Receptors, Progesterone/metabolism

KW - RNA, Messenger/genetics/metabolism

KW - Receptors, Estrogen/metabolism

KW - Antigens, Neoplasm/genetics/metabolism

KW - Breast Neoplasms/metabolism/mortality/pathology/therapy

KW - Carcinoma, Ductal, Breast/metabolism/mortality/pathology/therapy

KW - Carcinoma, Lobular/metabolism/mortality/pathology/therapy

KW - DNA Topoisomerases, Type II/genetics/metabolism

KW - GTPase-Activating Proteins/genetics/metabolism

KW - Ki-67 Antigen/genetics/metabolism