title: Automated quantitative analysis of E-cadherin expression in lymph node metastases is predictive of survival in invasive ductal breast cancer.
abstract: OBJECTIVE
  The tumor suppressor adhesion molecule E-cadherin is believed to have an anti-invasive role in breast cancer. Lymph node involvement is the best prognostic marker known, yet there is variability in outcome among node-positive patients. We investigated the relationship between E-cadherin expression in primary invasive ductal tumors and corresponding nodal metastases, and determined the prognostic value of E-cadherin expression in node-positive breast cancer.
  
  
  METHODS
  Membrane E-cadherin expression was studied by immunohistochemical staining of tissue microarrays with fluorescent-labeled antibodies. An objective method of automated quantitative analysis (AQUA) was used. AQUA uses cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and measures E-cadherin expression using a Cy5-conjugated antibody within the mask.
  
  
  RESULTS
  We employed a tissue microarray containing 207 primary and matched nodal metastases suitable for AQUA analysis. There was no significant difference in mean staining intensity between the primary and nodal specimens (P = 0.8). A scattergram was generated which identified a subset of patients (25%) with high E-cadherin expression in nodal metastases, and this top quartile had improved survival (P = 0.028). On univariate analysis, increased E-cadherin expression in nodal metastases was strongly associated with improved survival (P = 0.007), whereas expression in primary tumors was not (P = 0.13). On multivariate analysis, nodal E-cadherin expression retained its independent association with survival, as did tumor size and HER2/neu status.
  
  
  CONCLUSIONS
  Strong E-cadherin expression in lymph node metastases was highly predictive of improved survival. This suggests that expression of adhesion molecules at metastatic sites portends less aggressive tumor behavior.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Malini
authors.initials: M
authors.lastname: Harigopal
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Berger
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000295:instrumentation / Q000379:methods*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015820:Cadherins