Prognostic Role of Epithelial-Mesenchymal Transition (EMT) Markers SNAIL-1&Eph A2 Expressions in Breast Carcinoma

Background, The breast cancer is one of the commonest cancers worldwide and the commonest malignancy of females in Egypt. The understanding of the molecular pathways of its carcinogenesis is important to discover recent therapeutic targets. Epithelial-mesenchymal transition (EMT) is a recent explanation of cancer progression, metastases and the resistance to chemotherapy in breast cancer. EMT process is controlled by many pathways and markers and understanding their functions, role in metastases is needed to modify the treatment strategies for breast cancer patients. A recently discovered EMT-inducing transcription factors is snail-1, that was involved in cell proliferation, apoptosis, metastasis, drugs resistance, and several aspects of the carcinogenic process EphA2 protein is an essential component of RTK/Ras-signaling that are involved in EMT and cooperates with Wnt/b-catenin-pathway. Aim of the work, was to evaluate EMT markers Snail1& Eph A2 expressions in breast cancer patients correlating their expressions with clinicopathological parameters and patients outcome. Methods, EMT markers Snail-1& Eph A2 expressions were evaluated in sections from 60 paraffin blocks of breast cancer using immunohistochemistry. We analyzed correlations between the levels of their expressions, clinical, pathological parameters of the patients and patients outcome. Results, Snail1 overexpression and Eph A2 positive expression in breast cancer was associated with higher grade (less than0.03 and less than0.01 respectively), higher stage of the tumor, presence of lymph node metastases, distant metastasis, high KI67 labeling index, negative ER& PR hormonal receptors, high Her2 neu expression and aggressive molecular subtype like triple negative, luminal B and her2 neu amplified (pless than0.001 for all of them). The expression of both markers was significantly positively correlated with each other (pless than0.001). The 3-year overall survival rate was 86.5 % with a mean of 35.2 0.22 months (95 % CI, 35.2 36.1 months). There was a significant correlation between the progression and Snail-1 (Pless than0.02) and there were highly significant correlations between combination of both markers expression and overall survival and progression free survival (Pless than0.001). Conclusion, Snail1& Eph A2 are markers of poor prognosis of breast cancer patients with an impact on survival.