Date Published: June 20, 2019
Publisher: Public Library of Science
Author(s): Fabiola Giudici, Elisabetta Petracci, Oriana Nanni, Cristina Bottin, Maurizio Pinamonti, Fabrizio Zanconati, Bruna Scaggiante, Aamir Ahmad.
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.
Breast cancer is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide [1,2]. Prognostic factors include histological features (histological type, histological grade, lymphovascular invasion), tumor size, lymph node status, steroid hormone receptors status and age [3–5]. Molecular stratification based on gene expression profiling revealed that breast cancers could be classified in the so-called intrinsic subtypes-Luminal A, Luminal B, HER2-enriched, basal-like, and normal-like- , which correlate with the efficacy of chemotherapy and life expectancy .The St. Gallen International Expert Consensus proposed a method for classifying breast cancer into 4 subtypes using immunostaining: Luminal A, Luminal B, Human Epidermal growth factor Receptor 2 (HER2) positive and triple negative- type breast cancer (TNBC) . Approximately 15–20% of all breast cancers are triple-negative breast cancer (TNBC) due to the lack of expression of three proteins: estrogen receptor (ER), progesterone receptor (PR), and HER2 .
TNBC is a heterogeneous disease, highly variable with respect to its biology and etiology and more likely to be poorly differentiated; these cancers often display an aggressive clinical course . Moreover, due to the lack of specific cellular receptors in cancer cells, targeted therapies have not been established, and, as a result, TNBC mortality remains high [11,52]. Many studies documented a high rate of recurrence among TNBC patients [53,54]. In our TNBC cohort we found a distant recurrence rate of 36.90%, in agreement with literature data . The risk of distant recurrences appeared to be high in the first 1–4 years after diagnosis and treatment [54,55]: our findings confirmed this, as more than 70% of the recurrences occurred within 4 years, with a peak during the 1 year. In our TNBC cohort, on univariate analysis, tumor size, nodal status and stage were associated with DFS and BCSS, in agreement with a recent study [56,57]. Moreover, we found that women with a conservative surgery exhibited an improved BCSS in comparison to patients treated with mastectomy (univariate analysis) as recently shown by other authors [14,57].
In conclusion, our data showed that high expression levels of eEF1A2 protein in formalin-fixed paraffin-embedded TNBC tissues is associated with worse prognosis. These results encourage extending the study on eEF1A2 expression levels in a larger independent cohort of TNBC to evaluate its prognostic usefulness for the clinical practice and possibly as potential target for the therapy.