Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers
| Autor: | George Fountzilas, Ioannis Kostopoulos, Ioannis Kaklamanos, Kyriaki Papadopoulou, Helen Gogas, Kyriakos Koukoulias, Grigorios Rallis, Pavlos Papakostas, Dimitrios Bafaloukos, Dimitrios Pectasides, Sotiris Lakis, Vassiliki Kotoula, Evangelia Razis, Sofia Levva, Christos Papadimitriou, Kyriaki Manousou, Vasilios Karavasilis, Gerasimos Aravantinos, Flora Zagouri, Eufemia Balassi, George Pentheroudakis |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Anthracycline Genotype Triple Negative Breast Neoplasms Biochemistry Disease-Free Survival 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Genetics Carcinoma Medicine Humans EGFR Gene Amplification Epidermal growth factor receptor Molecular Biology In Situ Hybridization Fluorescence Aged Aged 80 and over biology business.industry Middle Aged medicine.disease Prognosis ErbB Receptors Gene Expression Regulation Neoplastic 030104 developmental biology Chemotherapy Adjuvant 030220 oncology & carcinogenesis Mutation biology.protein Immunohistochemistry Female Tumor Suppressor Protein p53 business Research Article |
| Zdroj: | Cancer genomicsproteomics. 14(3) |
| ISSN: | 1790-6245 |
| Popis: | Background: Epidermal growth factor receptor (EGFR) aberrations have been implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their impact on prognosis and, therefore, druggability, remain controversial. Herein, we studied EGFR aberrations at different molecular levels and assessed their prognostic impact in patients with operable TNBC treated with adjuvant anthracycline-based chemotherapy. Materials and Methods: We evaluated the prognostic impact of EGFR gene status by fluorescent in situ hybridization (FISH), EGFR coding mutations by Sanger and next-generation sequencing, relative EGFR messenger RNA (mRNA) levels by qPCR (upper quartile) and EGFR and p53 protein expression by immunohistochemistry (IHC), in 352 centrally-assessed tumors from an equal number of TNBC patients. Results: Approximately 53.5% of the tumors expressed EGFR, 59.3% p53 and 35.9% both EGFR and p53 proteins; 4.1% showed EGFR gene amplification and 4.4% carried EGFR mutations. The latter were located outside the druggable kinase domain region and presented at low frequencies. Amplification and mutations overlapped only in one case of glycogen-rich carcinoma. EGFR and CEN7 copies were higher in tumors from older patients (p=0.002 and p=0.003, respectively). Patients with amplified tumors (n=11) had excellent prognosis (0 relapses and deaths). Upon multivariate analysis, high EGFR copies conferred significantly favorable disease-free survival (HR=0.57, 95% CI 0.36-0.90, Wald’s p=0.017) and high CEN7 copies favorable overall survival (HR=0.49, 95% CI=0.29-0.83, Wald’s p=0.008). Patients with EGFR–/p53+ and EGFR+/p53– tumors had significantly higher risk for relapse than those with EGFR–/p53– and EGFR+/p53+ tumors (HR=1.73, 95% CI=1.12-2.67, Wald’s p=0.013). Conclusion: EGFR gene amplification and mutations are rare in TNBC, the latter of no apparent clinical relevance. Surrogate markers of EGFR-related chromosomal aberrations and combined EGFR/p53 IHC phenotypes appear to be associated with favorable prognosis in patients with operable TNBC receiving conventional adjuvant chemotherapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|