Expression of the Epithelial Mesenchymal Transition Regulator Snail in Matrix-Producing Carcinomas of the Breast
K Gwin, A Contreras, M Tretiakova, A Montag. University of Chicago Medical Center, Chicago, IL
Background: Epithelial mesenchymal transition (EMT) is defined as the dynamic transition from polarized, immotile epithelia to highly mobile, mesenchymal-like cells. EMT is hypothesized to promote metastasis of carcinomas, and is ultimately regulated by transcription factors such as Snail that downregulate epithelial and upregulate mesenchymal genes. The zinc-finger transcription factor Snail particularly functions in repression of E-Cadherin expression and cell migration. EMT is accompanied by a morphologic switch, as the polarized epithelial cells become more spindled and mesenchyme-like. However, EMT is thought to occur only in a small percentage of tumor cells at any one time. Therefore we hypothesized that matrix-producing carcinomas (MPC) of the breast, which reveal a mixed epithelial and mesenchymal component with a chondromyxoid matrix, may show EMT and increased expression of Snail throughout both tumor components.
Design: Archival paraffin embedded material of 12 MPCs and 1 lymph node metastases were examined by IHC for the expression and localization of Snail. Staining was evaluated for positivity in both the epithelial and chondroid metaplastic component. A minimum of 5% staining of the total tumor cell population was required for a positive result.
Results: Overall, 92% of the study cases revealed simultaneous nuclear and cytoplasmic positive staining in the conventional and metaplastic carcinoma component. Those tumor cells with metaplastic features were more likely to express nuclear staining, while the conventional carcinoma cells had a stronger correlation with cytoplasmic staining.
Snail expression in tumor cellsCA=Carcinoma component, LN= lymph node
|Location||Conventional CA||Metaplastic CA||LN|
Snail was not expressed in normal mammary tissue.
Conclusions: EMT is hypothesized to allow epithelial-derived tumors to acquire a more aggressive phenotype through the loss of epithelial cell polarity. During embryogenesis, Snail is involved in gastrulation and neural-crest migration, while in tumor progression, Snail has been observed to repress E-cadherin expression, allowing the acquisition of invasive and migratory properties that are critical for metastasis of carcinoma cells. Our findings suggest that the high expression rate of Snail in MPC may have an important function in EMT. The strong nuclear expression in the metaplastic component may play a role in the known high metastatic potential and aggressive behavior of MPC.
Monday, March 9, 2009 1:00 PM
Poster Session II # 40, Monday Afternoon