Jedrzej Grzegrzolka1, Martyna Biala1, Patrycja Wojtyra1, Christopher Kobierzycki2, Mateusz Olbromski1, Agnieszka Gomulkiewicz1, Aleksandra Piotrowska1, Janusz Rys3, Marzena Podhorska-Okolow1, Piotr Dziegiel4. 1. Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland. 2. Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland Department of Physiotherapy, University School of Physical Education, Wroclaw, Poland. 3. Department of Tumor Pathology, Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Krakow, Poland. 4. Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland Department of Physiotherapy, University School of Physical Education, Wroclaw, Poland piotr.dziegiel@umed.wroc.pl.
Abstract
BACKGROUND: The epithelial-mesenchymal transition (EMT) has been observed in progression of in situ breast cancer to the invasive form and might be initiated by snail family zinc finger 2 (SLUG) and twist family bHLH transcription factor 1 (TWIST) protein overexpression. During this phenomenon, cells lose their epithelial phenotype and acquire mesenchymal features. The aim of the study was to examine the association of EMT markers SLUG and TWIST with clinicopathological data and the possibility of using these proteins as prognostic markers of breast cancer. MATERIALS AND METHODS: Immunohistochemical analysis (IHC) of SLUG and TWIST expression was performed on archival paraffin samples of 19 cases with fibrocystic breast changes (control group), 148 cases of invasive ductal breast cancer (IDC) and 26 of invasive lobular breast cancer (ILC). Laser capture microdissection for isolation of cells from 17 frozen samples of IDC was employed and subsequently SLUG and TWIST mRNA expression in cancer and stromal cells was detected separately by real-time polymerase chain reaction. RESULTS: SLUG and TWIST expression in IDC was significant higher in stromal cells regardless of the method of quantification used (p<0.001 for SLUG mRNA, and p<0.0001 for SLUG IHC, TWIST IHC and TWIST mRNA expression). Positive correlation of SLUG and TWIST protein and mRNA expression was observed in stromal cells of IDC (r=0.347; p<0.0001 and r=0.704; p<0.01, respectively). Expression of TWIST protein in IDC was higher in cancer cells of cases with shorter event-free survival period, as well as in stromal cells of cases with shorter overall survival period (p<0.05 for both). CONCLUSION: Stromal cells could play a role in the regulation of EMT in breast cancer. Copyright
BACKGROUND: The epithelial-mesenchymal transition (EMT) has been observed in progression of in situ breast cancer to the invasive form and might be initiated by snail family zinc finger 2 (SLUG) and twist family bHLH transcription factor 1 (TWIST) protein overexpression. During this phenomenon, cells lose their epithelial phenotype and acquire mesenchymal features. The aim of the study was to examine the association of EMT markers SLUG and TWIST with clinicopathological data and the possibility of using these proteins as prognostic markers of breast cancer. MATERIALS AND METHODS: Immunohistochemical analysis (IHC) of SLUG and TWIST expression was performed on archival paraffin samples of 19 cases with fibrocystic breast changes (control group), 148 cases of invasive ductal breast cancer (IDC) and 26 of invasive lobular breast cancer (ILC). Laser capture microdissection for isolation of cells from 17 frozen samples of IDC was employed and subsequently SLUG and TWIST mRNA expression in cancer and stromal cells was detected separately by real-time polymerase chain reaction. RESULTS:SLUG and TWIST expression in IDC was significant higher in stromal cells regardless of the method of quantification used (p<0.001 for SLUG mRNA, and p<0.0001 for SLUG IHC, TWIST IHC and TWIST mRNA expression). Positive correlation of SLUG and TWIST protein and mRNA expression was observed in stromal cells of IDC (r=0.347; p<0.0001 and r=0.704; p<0.01, respectively). Expression of TWIST protein in IDC was higher in cancer cells of cases with shorter event-free survival period, as well as in stromal cells of cases with shorter overall survival period (p<0.05 for both). CONCLUSION: Stromal cells could play a role in the regulation of EMT in breast cancer. Copyright
Authors: Guetchyn Millien; Yuxia Cao; Carl J O'Hara; Jean-Bosco Tagne; Anne Hinds; Mary C Williams; Maria I Ramirez; Hasmeena Kathuria Journal: Clin Exp Metastasis Date: 2018-06-16 Impact factor: 5.150