TP53 mutations determined by targeted NGS in breast cancer: a case-control study
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Angeliki Andrikopoulou1, Evangelos Terpos1, Spyridoula Chatzinikolaou1, Kleoniki Apostolidou1, Ioannis Ntanasis-Stathopoulos1, Maria Gavriatopoulou1, Meletios-Athanasios Dimopoulos1 and Flora Zagouri1
1 Department of Clinical Therapeutics, Alexandra Hospital Medical School, Athens 11528, Greece
Keywords: TP53 mutations; next-generation sequencing; biomarker; prognosis; breast cancer
Received: July 15, 2021 Accepted: August 28, 2021 Published: October 12, 2021
Background: Tumor protein 53 (TP53) gene mutations are identified in up to 37% of breast tumors especially in HER-2 positive and basal-like subtype. Previous studies have indicated TP53 mutations as a prognostic biomarker in breast cancer. However, most of these studies performed immunohistochemistry (IHC) for the detection of TP53 mutations.
Aim: The purpose of our study is to evaluate the role of TP53 somatic mutations detected via next-generation sequencing (NGS) as a potential prognostic marker in patients with breast cancer.
Materials and Methods: 82 female patients with Stage I–III breast cancer underwent NGS in paraffin blocks and blood samples during the period 25/09/2019 through 25/05/2021. 23 cases of somatic TP53 mutations and 23 cases of healthy controls were matched on age at diagnosis, menopausal status, histological subtype, histological grade, ki67 expression and disease stage.
Results: Mean age at diagnosis was 52.35 (SD; 11.47) years. The somatic TP53 mutation NM_000546.5:c.824G>A p.(Cys275Tyr) was most frequently detected. Co-existence of PIK3CA mutation was a common finding in somatic TP53-mutant tumors (4/23; 17.4%). Disease-free survival was shorter in TP53-mutated cases (16.3 months vs. 62.9 months). TP53 pathogenic somatic mutations were associated with a 8-fold risk of recurrence in the univariate Cox regression analysis (OR = 8.530, 95% CI: 1.81–40.117; p = 0.007).
Conclusions: Our case-control study suggests that TP53 somatic mutations detected by next-generation sequencing (NGS) are associated with an adverse prognosis in breast cancer.
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