ZNF703 gene copy number and protein expression in breast cancer; associations with proliferation, prognosis and luminal subtypes
Autor: | Monica J. Engstrøm, Anna M. Bofin, Borgny Ytterhus, Joanna Ewa Sawicka, Elise Klæstad, Marit Valla |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Gene Dosage Breast Neoplasms 03 medical and health sciences 0302 clinical medicine Breast cancer Humans Medicine Cumulative incidence Copy-number variation Gene Lymph node In Situ Hybridization Fluorescence Cell Proliferation medicine.diagnostic_test business.industry Amplicon Prognosis medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female Carrier Proteins business Fluorescence in situ hybridization |
Zdroj: | Breast Cancer Research and Treatment. 186:65-77 |
ISSN: | 1573-7217 0167-6806 |
Popis: | 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. 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. 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. In breast cancer, high ZNF703 copy number is associated with increased proliferation, Luminal B subtypes and poor prognosis. |
Databáze: | OpenAIRE |
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