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Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables.
Mod Pathol. 2000 May; 13(5):542-7.MP

Abstract

Topoisomerase IIalpha (topo IIalpha) plays a key role in DNA replication and is a target for multiple chemotherapeutic agents. In breast cancer, topo II expression has been linked to cell proliferation and HER2/neu protein overexpression. However, its relationship with outcome variables is not well established. Formalin-fixed, paraffin-embedded primary breast cancers from 184 women (mean age, 60 years) were stained for topo II by automated immunohistochemistry. A topo II expression index (TI) was determined by counting the number of positive cells per high-power field and calculating an overall mean number of positive cells per high-power field. Tumors with a TI of more than 1 were considered positive, and those with a TI of 1 or less were considered negative. A cell proliferation index was determine d by automated immunohistochemistry using the MIB-1 antibody in an identical technique. HER-2/neu gene amplification (HER-2 amp) was determined by automated fluorescence in situ hybridization using the Ventana unique sequence probe. Fifty-nine (32%) of the tumors had a TI greater than 1. On univariate analysis, increased topo II expression correlated with decreased patient survival (p = .001), advanced tumor stage (p = .034), lymph node metastasis (p = .018), and HER-2 amp (p = .016). Tumor stage (p < .0001), node-positive status (p < .0001), tumor grade (p = .025), HER-2 amp (p < .0001), and MIB-1 overexpression (p = .002) also correlated with survival on univariate analysis. Topo II expression did not correlate with tumor size, grade, estrogen receptor/progesterone receptor status, or disease recurrence. On multivariate analysis, stage (p < .0001), lymph node metastasis (p < .0001), and tumor grade (p = .002) all independently predicted disease-related death. Increased topo II expression is associated with an aggressive form of breast cancer featuring HER-2 amp and predicts disease-related death, lymph node metastasis, and advanced tumor stage.

Authors+Show Affiliations

Department of Pathology, Albany Medical College, New York 12208, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10824926

Citation

Depowski, P L., et al. "Topoisomerase IIalpha Expression in Breast Cancer: Correlation With Outcome Variables." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 13, no. 5, 2000, pp. 542-7.
Depowski PL, Rosenthal SI, Brien TP, et al. Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables. Mod Pathol. 2000;13(5):542-7.
Depowski, P. L., Rosenthal, S. I., Brien, T. P., Stylos, S., Johnson, R. L., & Ross, J. S. (2000). Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 13(5), 542-7.
Depowski PL, et al. Topoisomerase IIalpha Expression in Breast Cancer: Correlation With Outcome Variables. Mod Pathol. 2000;13(5):542-7. PubMed PMID: 10824926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables. AU - Depowski,P L, AU - Rosenthal,S I, AU - Brien,T P, AU - Stylos,S, AU - Johnson,R L, AU - Ross,J S, PY - 2000/5/29/pubmed PY - 2000/7/15/medline PY - 2000/5/29/entrez SP - 542 EP - 7 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 13 IS - 5 N2 - Topoisomerase IIalpha (topo IIalpha) plays a key role in DNA replication and is a target for multiple chemotherapeutic agents. In breast cancer, topo II expression has been linked to cell proliferation and HER2/neu protein overexpression. However, its relationship with outcome variables is not well established. Formalin-fixed, paraffin-embedded primary breast cancers from 184 women (mean age, 60 years) were stained for topo II by automated immunohistochemistry. A topo II expression index (TI) was determined by counting the number of positive cells per high-power field and calculating an overall mean number of positive cells per high-power field. Tumors with a TI of more than 1 were considered positive, and those with a TI of 1 or less were considered negative. A cell proliferation index was determine d by automated immunohistochemistry using the MIB-1 antibody in an identical technique. HER-2/neu gene amplification (HER-2 amp) was determined by automated fluorescence in situ hybridization using the Ventana unique sequence probe. Fifty-nine (32%) of the tumors had a TI greater than 1. On univariate analysis, increased topo II expression correlated with decreased patient survival (p = .001), advanced tumor stage (p = .034), lymph node metastasis (p = .018), and HER-2 amp (p = .016). Tumor stage (p < .0001), node-positive status (p < .0001), tumor grade (p = .025), HER-2 amp (p < .0001), and MIB-1 overexpression (p = .002) also correlated with survival on univariate analysis. Topo II expression did not correlate with tumor size, grade, estrogen receptor/progesterone receptor status, or disease recurrence. On multivariate analysis, stage (p < .0001), lymph node metastasis (p < .0001), and tumor grade (p = .002) all independently predicted disease-related death. Increased topo II expression is associated with an aggressive form of breast cancer featuring HER-2 amp and predicts disease-related death, lymph node metastasis, and advanced tumor stage. SN - 0893-3952 UR - https://www.unboundmedicine.com/medline/citation/10824926/Topoisomerase_IIalpha_expression_in_breast_cancer:_correlation_with_outcome_variables_ L2 - https://doi.org/10.1038/modpathol.3880094 DB - PRIME DP - Unbound Medicine ER -