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.

miR-302a Inhibits Metastasis and Cetuximab Resistance in Colorectal Cancer by Targeting NFIB and CD44

“…Slides were mounted with Mounting Medium (Vectashield) before imaging with a Nikon ECLIPSE Ti confocal microscope. The staining intensity was assessed as previously described 19.…”

Changing molecular profile of brain metastases compared with matched breast primary cancers and impact on clinical outcomes

“…Epidermal growth factor receptor is a transmembrane receptor for members of the epidermal growth factor family, triggering cell proliferation. High EGFR has been associated with a poor prognosis in breast cancer ( Li et al , 2015 ) and linked to the development of breast cancer brain metastasis ( Hohensee et al , 2013 ), with roles in cell migration and invasion promoting brain metastasis ( Nie et al , 2012 ). EGFR positive breast cancer appears more commonly in patients with poorer prognosis grade 3 disease and oestrogen receptor negative tumours ( Stebbing et al , 2011 ).…”

Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk

“…The PI3K/Akt pathway leads to metabolic activity, including glucose uptake and decreased apoptosis, and the MAPK pathway leads to mitogenic activity [54]; both are main signaling cascades in controlling cellular process promoting carcinogenesis [55,56]. PIK3R1, AKT1/2, and MAPK1 genes are the key components of these pathways [26,55,[57][58][59], but the studies of their genetic variants in relation to cancer have been limited [12,[24][25][26][27].…”