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Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers.

ΤίτλοςPrognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers.
Publication TypeJournal Article
Year of Publication2017
AuthorsLevva, S., Kotoula V., Kostopoulos I., Manousou K., Papadimitriou C., Papadopoulou K., Lakis S., Koukoulias K., Karavasilis V., Pentheroudakis G., Balassi E., Zagouri F., Kaklamanos I. G., Pectasides D., Razis E., Aravantinos G., Papakostas P., Bafaloukos D., Rallis G., Gogas H., & Fountzilas G.
JournalCancer Genomics Proteomics
Volume14
Issue3
Pagination181-195
Date Published2017 May-Jun
ISSN1790-6245
Λέξεις κλειδιάAdult, Aged, Aged, 80 and over, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Genotype, Humans, In Situ Hybridization, Fluorescence, Middle Aged, Mutation, Prognosis, Receptor, Epidermal Growth Factor, Triple Negative Breast Neoplasms, Tumor Suppressor Protein p53
Abstract

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.

DOI10.21873/cgp.20030
Alternate JournalCancer Genomics Proteomics
PubMed ID28446533
PubMed Central IDPMC5420819

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