BRCA1 and TOP2A gene amplification and protein expression in four molecular subtypes of breast cancer

Olivera Mitrovic,Dragoslava Djikic,Tijana Brekovic,Vesna Koko,Sanja Vignjevic,Mileva Micic,Mirela Budec,V. Cokic

doi:10.2298/abs1302511m

Olivera Mitrovic, Dragoslava Djikic + Show 6 more

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https://doi.org/10.2298/abs1302511m

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Abstract

We studied TOP2A amplification (using FISH methods), and TOP2A and BRCA1 protein overexpression (immunohistochemistry) in four molecular subtypes of breast cancer. Of 53 patients, 32 showed TOP2A and 38 showed BRCA1 overexpression. The highest percentage of TOP2A amplification (47.8%) and deletion (13%) was detected in Luminal B subtypes. Of 11 Luminal B tumors with TOP2A amplification, 9 (81.8%) overexpressed TOP2A. BRCA1 protein overexpression showed significant positive correlation with TOP2A protein expression. BRCA1 and TOP2A proteins exhibited similar patterns of expression in Luminal B and triple-negative breast cancer, suggesting the same prognosis in those patients.

Highlights

According to immunohistochemical identification of three biological markers, there are four different subtypes of breast cancer: Luminal A (ER+ and/or progesterone receptor (PR)+, HER2-), Luminal B (ER+ and/or PR+, HER2+), HER-2 positive (ER- and/or PR, HER2+) and triple-negative breast cancer (ER- and/or PR, HER2-) (Bertolo et al, 2008, Marchio et al, 2008).Some of the most important biological markers associated with the prediction and prognosis for breast cancer therapy are Breast Cancer Type 1 Susceptibility Protein (BRCA1) and Topoisomerase II A (TOP2A) (Arriola et al, 2008, Miyoshi et al, 2008)
Little is known about the relationship of BRCA1 protein expression with the TOP2A gene and protein aberration in four molecular subtypes of breast cancer
Owing to TOP2A proximity to the BRCA1 gene on chromosome 17 we originally thought that gene and protein aberration are present in the same cancer cells

Summary

Introduction

Some of the most important biological markers associated with the prediction and prognosis for breast cancer therapy are BRCA1 and TOP2A (Arriola et al, 2008, Miyoshi et al, 2008). The TOP2A gene is located on the long arm of chromosome 17 and plays an important role in DNA replication, transcription and recombination (Arriola et al., 2008). BRCA1 gene mutations are responsible for about 40-45% of hereditary breast cancers, while in sporadic breast cancer those mutations are rare. Expression of BRCA1 protein is frequently reduced in sporadic breast cancer, suggesting a very important and wider role in mammary carcinogenesis (Miyoshi et al, 2008). Breast cancer with BRCA1 gene mutations has a high frequency of p53 gene mutations, usually linked to a negative estrogen and progesterone receptor status (Miyoshi et al, 2008)

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