The role of epithelial-mesenchymal transition markers in invasive breast cancer among patients of Arab descent.

Abstract

e13166 Background: Epithelial-mesenchymal transition (EMT) is the process wherein polarized and cohesive epithelial cells lose their epithelial characteristics and acquire a mesenchymal phenotype and proceed to the invasive form of the tumor. Numerous regulators play a role in the complex signaling pathways that mediate the EMT process. This study aims to investigate the immunohistochemical (IHC) expression of several EMT-related markers and their implications on the diagnosis and prognosis of breast cancer in a cohort of Arab descent women. Methods: Patients of Arab descent treated surgically for invasive and in-situ breast cancer between 2017-2020 were included in the study. Expressions of Ki-67, Transforming growth factor- β (TGF-β), NF-kappaB (NF-kB), Snail, Vimentin, E-cadherin (E-Cad), and B-catenin (B-Cat) were evaluated by IHC in tissue microarray slides, as per guidelines in the literature. We examined the association between the tumor markers and other clinicopathological variables and prognosis. Fisher's exact tests were utilized to compare categorical variables between groups. Results: One hundred eleven patients were included, 65.8% had invasive ductal carcinoma (IDC); 19.8% had invasive lobular carcinoma (ILC); 13.5% had both ductal and lobular features, and 0.9% had ductal carcinoma in situ. 91 (54.1%) were grade 2 and 303 (41.4%) were grade 3 tumors. Most tumors were ER positive (81.8%), PR positive (75.7%), and HER-2 negative (77.5%). The median age at diagnosis was 52 years. High TGF- β expression was associated with higher frequency of grade 3 tumors (p=0.036), AJCC stage III (p=0.042), and larger tumor size (p=0.036) compared to those with low TGF-B expression. Patients with positive B-Cat expression had a higher risk of death compared to those with negative B-Cat expression (HR, 3.90; 95% CI, 1.19 to 15.93; p=0.024). IDC had a statistically significant increased expression of TGF-B (69.9% vs.45.5%, p=0.045), E-Cad (76.7% vs. 13.6%, p<0.001), and B-Cat (P 39.7% vs. 0%, p<0.001) when compared to ILC. The overall survival at 1 and 5 years were 96.3% (95% CI, 92.7-99.9) and 81.7% (95% CI, 73.8-90.3), respectively. Conclusions: Tumors with high expression for TGF- β and B-Cat exhibit more aggressive clinical behavior, suggesting the potential prognostic and therapeutic value of these markers. Due to the limited research focused on Arab descent women, findings from this study may provide the foundation for more extensive molecular and clinical studies to assess the validity and clinical utility of these biomarkers in breast cancer patients from diverse ethnic backgrounds.