title: Epidermal growth factor receptor and AKT1 gene copy numbers by multi-gene fluorescence in situ hybridization impact on prognosis in breast cancer.
abstract: The epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway aberrations play significant roles in breast cancer occurrence and development. However, the status of EGFR and AKT1 gene copy numbers remains unclear. In this study, we showed that the rates of EGFR and AKT1 gene copy number alterations were associated with the prognosis of breast cancer. Among 205 patients, high EGFR and AKT1 gene copy numbers were observed in 34.6% and 27.8% of cases by multi-gene fluorescence in situ hybridization, respectively. Co-heightened EGFR/AKT1 gene copy numbers were identified in 11.7% cases. No changes were found in 49.3% of patients. Although changes in EGFR and AKT1 gene copy numbers had no correlation with patients' age, tumor stage, histological grade and the expression status of other molecular makers, high EGFR (P = 0.0002) but not AKT1 (P = 0.1177) gene copy numbers correlated with poor 5-year overall survival. The patients with co-heightened EGFR/AKT1 gene copy numbers displayed a poorer prognosis than those with tumors with only high EGFR gene copy numbers (P = 0.0383). Both Univariate (U) and COX multivariate (C) analyses revealed that high EGFR and AKT1 gene copy numbers (P = 0.000 [U], P = 0.0001 [C]), similar to histological grade (P = 0.001 [U], P = 0.012 [C]) and lymph node metastasis (P = 0.046 [U], P = 0.158 [C]), were independent prognostic indicators of 5-year overall survival. These results indicate that high EGFR and AKT1 gene copy numbers were relatively frequent in breast cancer. Co-heightened EGFR/AKT1 gene copy numbers had a worse outcome than those with only high EGFR gene copy numbers, suggesting that evaluation of these two genes together may be useful for selecting patients for anti-EGFR-targeted therapy or anti-EGFR/AKT1-targeted therapy and for predicting outcomes.
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Su
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Bai
authors.affiliation: Beijing Union Medical College Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Beijing Union Medical College Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Linping
authors.initials: L
authors.lastname: Hu
authors.affiliation: Beijing Union Medical College Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Clinical Pathology Department of Karolinska Hospital, Karolinska Institute, Solna, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Zetterberg
authors.affiliation: Department of OB/GYN, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT1; breast cancer; epidermal growth factor receptor; gene copy number; survival analysis