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DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer

The α isoform of Topoisomerase IIα (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIα expression level and chemosensitivity of target cancer cells. To verify thi...

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Autores principales: MacGrogan, G, Rudolph, P, Mascarel, I de, Mauriac, L, Durand, M, Avril, A, Dilhuydy, J M, Robert, J, Mathoulin-Pélissier, S, Picot, V, Floquet, A, Sierankowski, G, Coindre, J M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376904/
https://www.ncbi.nlm.nih.gov/pubmed/12915875
http://dx.doi.org/10.1038/sj.bjc.6601185
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author MacGrogan, G
Rudolph, P
Mascarel, I de
Mauriac, L
Durand, M
Avril, A
Dilhuydy, J M
Robert, J
Mathoulin-Pélissier, S
Picot, V
Floquet, A
Sierankowski, G
Coindre, J M
author_facet MacGrogan, G
Rudolph, P
Mascarel, I de
Mauriac, L
Durand, M
Avril, A
Dilhuydy, J M
Robert, J
Mathoulin-Pélissier, S
Picot, V
Floquet, A
Sierankowski, G
Coindre, J M
author_sort MacGrogan, G
collection PubMed
description The α isoform of Topoisomerase IIα (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIα expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 cm and T(3) N(0–1) M(0) breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIα. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3–6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41–7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58–9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43–7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIα expression and tumour chemosensitivity and thus may have important practical implications.
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spelling pubmed-23769042009-09-10 DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer MacGrogan, G Rudolph, P Mascarel, I de Mauriac, L Durand, M Avril, A Dilhuydy, J M Robert, J Mathoulin-Pélissier, S Picot, V Floquet, A Sierankowski, G Coindre, J M Br J Cancer Molecular and Cellular Pathology The α isoform of Topoisomerase IIα (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIα expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 cm and T(3) N(0–1) M(0) breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIα. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3–6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41–7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58–9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43–7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIα expression and tumour chemosensitivity and thus may have important practical implications. Nature Publishing Group 2003-08-18 2003-08-12 /pmc/articles/PMC2376904/ /pubmed/12915875 http://dx.doi.org/10.1038/sj.bjc.6601185 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular and Cellular Pathology
MacGrogan, G
Rudolph, P
Mascarel, I de
Mauriac, L
Durand, M
Avril, A
Dilhuydy, J M
Robert, J
Mathoulin-Pélissier, S
Picot, V
Floquet, A
Sierankowski, G
Coindre, J M
DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer
title DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer
title_full DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer
title_fullStr DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer
title_full_unstemmed DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer
title_short DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer
title_sort dna topoisomerase iiα expression and the response toprimary chemotherapy in breast cancer
topic Molecular and Cellular Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376904/
https://www.ncbi.nlm.nih.gov/pubmed/12915875
http://dx.doi.org/10.1038/sj.bjc.6601185
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