[232] Epithelial-Mesenchymal Transition Cells Are Enriched after Hormonal Therapy

X Li, J Huang, Q Zhai, MT Lewis, MR Schwartz, J Chang. The Methodist Hospital, Houston, TX; Baylor College of Medicine, Houston, TX

Background: Epithelial-mesenchymal transition (EMT) is a multi-step process in which cells reorganize cytoskeleton, lose cell-cell junctions, and acquire mesenchymal spindle-shaped morphology. EMT is thought to promote the progession and invasion of cancer cells. The role of EMT in cancer progression and metastasis has been specifically demonstrated in breast cancer. A set of EMT gene signatures has been identified including up-regulation of vimentin, MMP2/3 and down-regulation of E-cadherin. Our unpublished data and other studies suggest that the EMT pathway may be involved in breast cancer stem cell development and proliferation. We have previously shown that breast cancer stem cells are resistant to chemotherapy and hormonal therapy, and that the stem cell population is increased after these treatments. Our aim in this study was to evaluate whether EMT cells are also enriched after conventional treatment.
Design: Twenty-three (23) paired ER positive paraffin embedded breast cancer samples before and 3 months after letrozole treatment were stained with vimentin and E-cadherin using an immunohistochemical (IHC) method. Positivity was evaluated using the Allred scoring scheme. Immunofluorescence co-staining using vimentin and pan-cytokeratin in biopsy samples was used to confirm the co-expression of vimentin and pan-cytokeratin in tumor cells. We also measured the MMP2 RNA level, using Q-RTPCR, in samples from 60 patients before, 10-14 days and 3 months after letrozle treatment.
Results: IHC demonstrated significant enrichment of vimentin expressing tumor cells after letrozole treament (P<0.05). Immunofluorescence studies confirmed the co-expression of pan-cytokeratin and vimentin in tumor cells. The MMP2 RNA level was significantly increased at 10-14 days and 3 months after letrozole treament (P<0.0001 and P<0.00001, respectively) compared with pre-treatement samples. However, we did not find a decrease of E-cadherin expression in post letrozole treatment samples using IHC, which may be due to the low baseline level of E-cadherin in the tumor cells.
Conclusions: The association of EMT with treatment resistance has been inferred by several articles. We and others have shown the EMT pathway may be involved in breast cancer stem cell development and proliferation. We herein provide the first direct clinical evidence that EMT cells are enriched following conventional therapy and the EMT pathways may be associated with treatment resistance.
Category: Breast

Monday, March 9, 2009 1:00 PM

Poster Session II # 57, Monday Afternoon