title: Epithelial cell identity in hyperplastic precursors of breast cancer.
abstract: BACKGROUND
  In the adult human breast, hyperplastic enlarged lobular unit (HELU) and atypical ductal hyperplasia (ADH) are two common abnormalities that frequently coexist with ductal carcinoma in situ (DCIS). For this reason, they have been proposed as the early steps in a biological continuum toward breast cancer.
  
  
  METHODS
  We investigated in silico the expression of 369 genes experimentally recognized as involved in establishing and maintaining epithelial cell identity and mammary gland remodeling, in HELUs or ADHs with respect to the corresponding patient-matched normal tissue.
  
  
  RESULTS
  Despite the common luminal origin, HELUs and ADHs proved to be characterized by distinct gene profiles that overlap for 5 genes only. While HELUs were associated with the overexpression of progesterone receptor (PGR), ADHs were characterized by the overexpression of estrogen receptor 1 (ESR1) coupled with the overexpression of some proliferation-associated genes.
  
  
  CONCLUSIONS
  This unexpected finding contradicts the notion that in differentiated luminal cells the expression of estrogen receptor (ER) is dissociated from cell proliferation and suggests that the establishing of an ER-dependent signaling is able to sustain cell proliferation in an autocrine manner as an early event in tumor initiation. Although clinical evidence indicates that only a fraction of HELUs and ADHs evolve to invasive cancer, present findings warn that exposure to synthetic progestins, frequently administered as hormone-replacement therapy, and estrogens, when abnormally produced by adipose cells and persistently present in the stroma surrounding the mammary gland, may cause these hyperplastic lesions.
authors.affiliation: Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. danila.coradini@gmail.com.
authors.forename: Danila
authors.initials: D
authors.lastname: Coradini
authors.affiliation: Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. patrizia.boracchi@unimi.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Boracchi
authors.affiliation: Senology Center, Ambrosiana Clinic, Cesano Boscone, Milan, 20090, Italy. saroriana@hotmail.it.
authors.forename: Saro
authors.initials: S
authors.lastname: Oriana
authors.affiliation: Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. elia.biganzoli@unimi.it.
authors.forename: Elia
authors.initials: E
authors.lastname: Biganzoli
authors.affiliation: Department of Clinical Sciences and Community Health, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, Milan, 20133, Italy. federico.ambrogi@unimi.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Ambrogi
mesh_terms: D000273:Adipose Tissue; D000328:Adult; D001940:Breast; D001943:Breast Neoplasms; D002278:Carcinoma in Situ; D002285:Carcinoma, Intraductal, Noninfiltrating; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells; D047628:Estrogen Receptor alpha; D004967:Estrogens; D006801:Humans; D006965:Hyperplasia; D042361:Mammary Glands, Human; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone