Epithelial-mesenchymal Transition Factor and Its Association With Mammographic Density and Breast Cancer Prognosis

Background/Aim: The tumor microenvironment influences tumor progression, invasion, and metastasis. This study determined the expression levels of epithelialmesenchymal transition (EMT) factors according to zone and their correlation with mammographic breast density and investigated the prognostic value of EMT factors. Patients and Methods: The clinical and pathological data of invasive carcinoma and ductal carcinoma in situ were reviewed. Primary breast tissue samples were evaluated using immunohistochemistry (IHC) staining of the EMTassociated markers, including alpha-SMA, vimentin, MMP-9, and CD34. The expression levels were analyzed in three areas: the tumor center, interface, and distal zones. EMT factors were correlated with mammographic breast density and oncologic outcomes. Results: An overall EMT phenotype conversion from positive to negative was seen in 55.7% of alpha-SMA- and 34.4% of MMP-9-positive cells between the tumor center and interface zones, which was significantly different (p<0.05). Most changes in EMT expression from the center to the distal zone were from positive to negative, but 23.0% of CD34-expressing cells showed negative to positive conversion. The proportion of alpha-SMA, vimentin, and MMP-9 expression was higher in the non-dense breast group compared to the dense breast group in the interface and distal zones (p<0.05). CD34 expression in the distal zone was an independent favorable prognostic factor for disease-free survival (p=0.039). Conclusion: The differential expression of EMT markers in each zone suggests heterogeneous cancer cell populations within each zone of breast cancer. EMT factor expression can also interplay between breast density stroma and geographical tumor zone.