title: Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1.
abstract: OBJECTIVE
  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 plexin B1, a cell-surface receptor for the semaphorin Sema4D (CD 100). However, the biological role of plexin B1 in breast cancer is largely unknown.
  
  
  METHODS
  Expression data of plexin B1 were obtained from Affymetrix microarray analysis of n = 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.
  
  
  RESULTS
  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, P = 0.0062; ER positive, P = 0.0107) and multivariate analyses (all patients, P = 0.032; ER positive, P = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Rody
authors.forename: Uwe
authors.initials: U
authors.lastname: Holtrich
authors.forename: Regine
authors.initials: R
authors.lastname: Gaetje
authors.forename: Mathias
authors.initials: M
authors.lastname: Gehrmann
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Raihanatou
authors.initials: R
authors.lastname: Diallo-Danebrock
authors.forename: Eugen
authors.initials: E
authors.lastname: Ruckhäberle
authors.forename: Dirk
authors.initials: D
authors.lastname: Metzler
authors.forename: Andre
authors.initials: A
authors.lastname: Ahr
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D039961:Semaphorins