Data from Poor Outcome in Estrogen Receptor–Positive Breast Cancers Predicted by Loss of <i>Plexin B1</i>

<div>Abstract<p><b>Purpose:</b> A common characteristic of mammary carcinomas is an inverse relationship between the estrogen receptor (ER) status and the proliferative activity of the tumor. Yet, a subset of ER-positive breast cancers is characterized by a high proliferation, suggesting malfunctions in ER responsiveness that influence the biological and therapeutic behavior of tumor cells. The expression of several ER-dependent genes seems to be dysregulated among those “uncoupled” tumors. One of those genes is <i>plexin B1</i>, a cell-surface receptor for the semaphorin Sema4D (CD 100). However, the biological role of plexin B1 in breast cancer is largely unknown.</p><p><b>Experimental Design:</b> Expression data of plexin B1 were obtained from Affymetrix microarray analysis of <i>n</i> = 119 breast cancer specimens. Validation was done by quantitative real-time PCR and protein expression was evaluated by immunohistochemistry. Expression data were compared with clinical characteristics as well as follow-up data of the disease.</p><p><b>Results:</b> Low plexin B1 expression levels characterize a more aggressive tumor phenotype. The expression of plexin B1 is strongly correlated with the ER status. However, even among ER-positive tumors, loss of plexin B1 is associated with an impaired prognosis of breast cancer patients in both univariate (all patients, <i>P</i> = 0.0062; ER positive, <i>P</i> = 0.0107) and multivariate analyses (all patients, <i>P</i> = 0.032; ER positive, <i>P</i> = 0.022). Immunohistochemistry reveals that the tumor cells themselves and not the endothelial cells are the major source of plexin B1 expression in the tumor.</p><p><b>Conclusion:</b> Plexin B1 acts not only as a new important prognostic but should also represent a predictive marker indicating an endocrine resistance. These data give a new insight in markers that could be involved in endocrine dysregulation of breast cancer.</p></div>