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Breast Cancer Research and Treatment

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01-02-2021 | Fluorescence in Situ Hybridization | Preclinical study

ZNF703 gene copy number and protein expression in breast cancer; associations with proliferation, prognosis and luminal subtypes

Authors: Elise Klæstad, Joanna Ewa Sawicka, Monica Jernberg Engstrøm, Borgny Ytterhus, Marit Valla, Anna Mary Bofin

Published in: Breast Cancer Research and Treatment | Issue 1/2021

Abstract

Purpose

Amplification of 8p12 is frequent in breast cancer and associated with poor prognosis in luminal subtypes. ZNF703 has been identified as the driver gene of proliferation in the A1 amplicon situated in 8p12. In this study, the aims were to investigate associations between ZNF703 copy number alterations and molecular subtypes, proliferation and prognosis, and using immunohistochemistry, examine associations between ZNF703 copy number and ZNF703 protein expression.

Methods

Copy number alterations in 702 primary breast tumours and corresponding lymph node metastases were examined using fluorescence in situ hybridization with probes for ZNF703 and centromere 8. In addition, protein expression was studied in 869 tumours from the same cohort. Associations between copy number alterations and protein expression and tumour characteristics were assessed using Pearson chi square test. The prognostic impact of ZNF703 copy number increase and protein expression was assessed estimating cumulative incidence of breast cancer death and hazard ratios.

Results

We found mean ZNF703 copy number ≥ 6 in 7% of tumours, most frequently in Luminal B subtypes. We found a positive association between increased copy number, and high proliferation, high histological grade, and poor prognosis. Luminal A tumours with high copy number had high histological grade and poor prognosis (borderline significant). We found positive nuclear staining in 76% of primary tumours. There was an association between copy number status and protein expression, but no association between protein expression and prognosis.

Conclusions

In breast cancer, high ZNF703 copy number is associated with increased proliferation, Luminal B subtypes and poor prognosis.

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Title: ZNF703 gene copy number and protein expression in breast cancer; associations with proliferation, prognosis and luminal subtypes
Authors: Elise Klæstad
Joanna Ewa Sawicka
Monica Jernberg Engstrøm
Borgny Ytterhus
Marit Valla
Anna Mary Bofin
Publication date: 01-02-2021
Publisher: Springer US
Keywords: Fluorescence in Situ Hybridization
Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 1/2021
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-06035-0

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