Epithelial Mesenchymal Transition (EMT) in Metastatic Breast Cancer in Omani Women

Abstract

Breast cancer (BC) in Oman affects younger women and has a more aggressive course. Clinical and biological variables like age, pregnancy, tumor size, type, grade, receptor expression and proliferation predict disease aggression but there is no direct predictor of metastasis except lymphovascular invasion. Epithelial-mesenchymal transition (EMT) is characterized by epithelial cells losing epithelial and acquiring mesenchymal morpho-immunophenotypic characteristics. In tumors, EMT-like transitions may signify a metastatic phenotype and have features in common with cancer stem cells (CSC) which show resistance to chemotherapy. This study aimed to identify EMT and CSC phenotypes in metastatic and non-metastatic breast cancer in Omani women and their association with conventional clinico-pathological predictors of BC. In a retrospective study of ninety-six Omani women with breast cancer, the association of age, pregnancy/lactation, tumor size, type, grade, ductal carcinoma insitu (DCIS), lymphovascular invasion, hormone/ HER2 receptor expression and Ki67 proliferation index (Ki67 PI) was tested with EMT/ CSC phenotype and metastasis. Young age ≤ 40 years, lymphovascular invasion and EMT had a strong association with metastasis; CSC approached significance. Vimentin expression in tumor cells, fibronectin and MMP-11 in stroma were reliable markers of EMT; dual EMT and CSC phenotype (Vim+/ CD44+/ CD 24-/low) had a strong association with apocrine variant, basal-like tumors and triple negative cancers. EMT had a strong association with Ki67 proliferation index (PI) and CSC with HER2-like tumors and distant metastasis. These select markers may be useful in metastasis-prediction in pre-treatment biopsies.

Immunohistochemical expression of vimentin in invasive breast carcinoma and its correlation with clinicopathological parameters

“…The study done by Lakhtakia et al . showed that there is a strong correlation between LVI and vimentin expression 23. In the present study, in TNBC cases, the association between vimentin expression and the status of LVI and higher tumor grade was statistically significant.…”

Silencing long noncoding RNA OGFRP1 inhibits the proliferation and migration of cervical carcinoma cells

“…28 The expression of Vimentin not only marks the EMT on tumour cells, but also lead to changes in morphology, motor ability, and adhesion ability: all of these are favourable for metastasis. 28 The expression of Vimentin not only marks the EMT on tumour cells, but also lead to changes in morphology, motor ability, and adhesion ability: all of these are favourable for metastasis.…”

“…Some biomarkers have been used to prove EMT, including membrane proteins like E-cadherin show reduced expression or are converted to N-cadherin. 28 The expression of Vimentin not only marks the EMT on tumour cells, but also lead to changes in morphology, motor ability, and adhesion ability: all of these are favourable for metastasis. 29 And the Snail family can reduce the expression of E-cadherin, cytokeratins, and increase the expression of mesenchyme.…”

The Difference of Expression of 18 Genes in Axillary Invasion and Vascular Invasion Compared to Control Samples in Breast Cancer

“…In epithelial tumors such as breast tumor, the epithelial-mesenchymal transition (EMT) phenomenon can appropriately explain the processes of distant metastasis (10). Recent studies from gene profiling have revealed some genes that can be overexpressed within the EMT process causing its activation and leading to tumor progression and metastasis (11, 12). Moreover, the expression of these genes in the EMT process may be associated with other tumor-related behaviors including vascular and lymphatic invasions which play a critical role in planning distant metastasis (13).…”