Elevated levels of eEF1A2 protein expression in triple negative breast cancer relate with poor prognosis

Abstract

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a translation factor selectively expressed by heart, skeletal muscle, nervous system and some specialized cells. Its ectopic expression relates with tumorigenesis in several types of human cancer. No data are available about the role of eEF1A2 in Triple Negative Breast Cancers (TNBC). This study investigated the relation between eEF1A2 protein levels and the prognosis of TNBC. A total of 84 TNBC diagnosed in the period 2002-2011 were included in the study. eEF1A2 protein level was measured in formalin-fixed paraffin-embedded tissues by immunohistochemistry in a semi-quantitative manner (sum of the percentage of positive cells x staining intensity) on a scale from 0 to 300. Cox regression assessed the association between eEF1A2 levels and disease-free survival (DFS) and breast cancer-specific survival (BCSS). Elevated values of eEF1A2 were associated with older age at diagnosis (p = 0.003), and androgen receptors positivity (p = 0.002). At univariate Cox analysis, eEF1A2 levels were not significantly associated with DFS and BCSS (p = 0.11 and p = 0.08, respectively) whereas adjusting for stage of disease, elevated levels of eEF1A2 protein resulted associated with poor prognosis (HR = 1.05, 95% CI: 1.01-1.11, p = 0.04 and HR = 1.07, 95% CI: 1.01-1.14, p = 0.03 for DFS and BCSS, respectively). This trend was confirmed analyzing negative versus positive samples by using categorized scores. Our data showed a negative prognostic role of eEF1A2 protein in TNBC, sustaining further investigations to confirm this result by wider and independent cohorts of patients.

Fig 1. Immunohistochemical expression of eEF1A2 in breast cancer.

a: absence of expression (0); b: weak expression (1+); c: moderate expression (2+); d: strong expression (3+). 20x magnification.

Fig 2. Expression of eEF1A2 in normal breast parenchyma.

a: expression in acinar cells; b: expression in ductal cells; c: weak (1+) expression in normal ductal cells used to calibrate staining intensity in cancer cells (2+). 20x magnification.

Fig 3. Flow-chart of the patient cohort included in this study.

Fig 4

Box plots of eEF1A2 values according to presence (in the left) or exclusion (in the right) of 0 values.

Fig 5

Estimated disease-free survival (A-C) and breast cancer specific survival (B-D) according to eEF1A2 dichotomizations. In panels A and B, a patient is considered eEF1A2 negative if the sum of the percentage of cells staining absent [0] and of the percentage of cells staining weakly [1+] is greater than the sum of the percentage of cells staining moderately [2+] and strongly [3+]; in panels C and D, a patient was considered eEF1A2 negative if it had no expression of eEF1A2 (100% expression at 0 or 1+), and positive otherwise.