Metastatic Breast Cancer Survival according to HER2 and Topo2a Gene Status

N Todorović-Raković,D Nikolić-Vukosavljević,Z Nešković-Konstantinović

doi:10.1155/2009/808947

N Todorović-Raković, D Nikolić-Vukosavljević + Show 1 more

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https://doi.org/10.1155/2009/808947

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Journal: Disease Markers	Publication Date: Jan 1, 2009
Citations: 6	License type: CC BY 3.0

Affiliation: Oncology Institute of Vojvodina

Abstract

The aim of this study was to determine the relationship between amplification of HER2 (Human epidermal growth factor receptor 2) and Topo2a (topoisomerase 2a) and their influence on prognosis in metastatic breast cancer (MBC) patients. Amplification of both HER2 and Topo2a genes was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue of 71 MBC patients. Starting point for follow-up was the time of diagnosis of metastatic disease. Although there was significant correlation between HER2 amplification and Topo2a alterations, Topo2a amplification was not strictly related to HER2 amplification. Follow-up of patients showed that there was no difference in MBC survival between HER2-nonamplified and HER2-amplified patients for subgroup as whole, but there was significant difference in MBC survival between patients with and without Topo2a amplification. HER2 amplification showed prognostic value in subgroups of patients, as well as Topo2a. Combination of these two genes with different status (nonamplified, amplified, coamplified) indicated that they might have additive effect. Also, it has been shown that Topo2a-amplified cases have poorer survival than Topo2a-nonamplified, when treated with CMF therapy.Topo2a amplification seems to be more promising biomarker of MBC survival, than HER2, and potential marker of resistance to CMF therapy.

Highlights

Metastatic breast cancer as a final stage of breast cancer, is a result of the biological expression of multiple genetic changes
There was a significant correlation between HER2 amplification and Topo2a gene alterations (Table 1)
When performing chromogenic in situ hybridization (CISH), 3–5 copies per nucleus is considered as possible aneuploidy and in all CISH studies aneuploidy is not treated as a cause of significant protein overexpression

Summary

Introduction

Metastatic breast cancer as a final stage of breast cancer, is a result of the biological expression of multiple genetic changes. Among these genetic alterations, gene amplification is the most frequent and represent important mechanism for oncogene overexpression in malignant tumor. A growth factor receptor gene HER2 was considered as target gene for amplification in chromosome 17 (amplicon) it is well known that HER2 is not the only gene that is amplified in the so called HER2 overexpression cluster [1]. It is possible that altered expression of these coamplified genes might have biological relevance and clinical significance in breast cancer. Topo2a gene is located adjacent to the HER2 oncogene at the chromosome 17. Topo2a is DNA-modifying enzyme that can pass segment of DNA duplex through reversibile enzyme-mediated double-strand break [5]

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