Cornelia Leo1, Christine Cotic2, Victoria Pomp3, Daniel Fink4, Zsuzsanna Varga5. 1. Department of Gynecology, Kantonsspital Baden, Baden, Switzerland. Electronic address: cornelia.leo@ksb.ch. 2. Department of Gynecology, University Hospital Zurich, 8010 Zurich, Switzerland. Electronic address: christine.cotic@usz.ch. 3. Department of Pathology and Molecularpathology, University Hospital Zurich, 8010 Zurich, Switzerland. 4. Department of Gynecology, University Hospital Zurich, 8010 Zurich, Switzerland. Electronic address: daniel.fink@usz.ch. 5. Department of Pathology and Molecularpathology, University Hospital Zurich, 8010 Zurich, Switzerland. Electronic address: zsuzsanna.varga@usz.ch.
Abstract
BACKGROUND: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers. It is associated with a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. Since TNBC lacks the expression of estrogen and progesterone receptors and Her2 status is also negative, there is currently no target that can be used for systemic therapy. Epithelial-mesenchymal transition (EMT) plays an important role in tumor progression and metastasis. In this study, we examined a subset of EMT markers consisting of Snail, Twist-1 and Lox in TNBC and non-TNBC breast cancer subtypes and analyzed their expression pattern in regard to subtype, clinico-pathological parameters and prognosis. EXPERIMENTAL DESIGN: We analyzed 659 breast cancer samples from two tissue microarrays. Breast cancer samples were categorized into two groups according to hormone receptor expression and Her2 status (n = 146 were triple negative, n = 513 were non triple-negative). Immunohistochemical expression of Snail, Twist-1 and Lox was semi-quantitatively analyzed using a three-tiered (weak-moderate-strong) scoring system. Results were statistically analyzed and correlated to clinico-pathological parameters and overall survival. RESULTS: Strong overexpression of Lox was significantly higher in triple negative breast cancers when compared to non triple-negative breast cancers (p < 0.001). No difference was seen between the groups regarding Snail and Twist expression (p > 0.05). In addition, Lox expression was significantly stronger in poorly differentiated (G3) breast cancers (p < 0.001 for Lox). CONCLUSIONS: The EMT marker Lox has a differential expression pattern in breast cancer, being significantly overexpressed in triple negative breast cancers. We could not link this expression to prognosis, however, this marker might be explored in future studies as possible target for systemic therapy of TNBC.
BACKGROUND: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers. It is associated with a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. Since TNBC lacks the expression of estrogen and progesterone receptors and Her2 status is also negative, there is currently no target that can be used for systemic therapy. Epithelial-mesenchymal transition (EMT) plays an important role in tumor progression and metastasis. In this study, we examined a subset of EMT markers consisting of Snail, Twist-1 and Lox in TNBC and non-TNBC breast cancer subtypes and analyzed their expression pattern in regard to subtype, clinico-pathological parameters and prognosis. EXPERIMENTAL DESIGN: We analyzed 659 breast cancer samples from two tissue microarrays. Breast cancer samples were categorized into two groups according to hormone receptor expression and Her2 status (n = 146 were triple negative, n = 513 were non triple-negative). Immunohistochemical expression of Snail, Twist-1 and Lox was semi-quantitatively analyzed using a three-tiered (weak-moderate-strong) scoring system. Results were statistically analyzed and correlated to clinico-pathological parameters and overall survival. RESULTS: Strong overexpression of Lox was significantly higher in triple negative breast cancers when compared to non triple-negative breast cancers (p < 0.001). No difference was seen between the groups regarding Snail and Twist expression (p > 0.05). In addition, Lox expression was significantly stronger in poorly differentiated (G3) breast cancers (p < 0.001 for Lox). CONCLUSIONS: The EMT marker Lox has a differential expression pattern in breast cancer, being significantly overexpressed in triple negative breast cancers. We could not link this expression to prognosis, however, this marker might be explored in future studies as possible target for systemic therapy of TNBC.