title: Fluorescence in situ hybridization of ductal lavage samples identifies malignant phenotypes from cytologically normal cells in women with breast cancer.
abstract: BACKGROUND
  Ductal lavage (DL) does not routinely identify cytologically malignant cells. For this study, the authors asked whether molecular analyses of DL specimens from women with cancer would identify abnormal cells, even if they appeared cytologically normal.
  
  
  METHODS
  DL was performed and yielded fluid in 29 of 45 consenting women who were undergoing breast cancer surgery. Array comparative genomic hybridization (CGH) was performed on the corresponding tumor tissue from 14 women. There was no single, common alteration; thus, bacterial artificial chromosome-specific fluorescence in situ hybridization (FISH) probes were selected based on CGH alterations.
  
  
  RESULTS
  FISH copy number changes were detected in tumor sections in 9 women. In the corresponding 9 DL samples, 1 sample was clearly malignant on cytology, 1 showed marked atypia, 1 showed mild atypia, and the rest were benign. Five of the 9 DL samples had epithelial cells that showed genetic changes identical to those observed in the tumor by FISH. The remaining 4 of 9 DL samples that did not show molecular changes were probably (N = 1) or possibly (N = 3) from the same duct as the tumor.
  
  
  CONCLUSIONS
  Although only 11% of the DL samples were identified as malignant cytologically, 55% showed molecular changes that were identical to those observed in the tumor. FISH was more sensitive for finding tumor in DL specimens than cytology. However, the ductal system in which the tumor was located did not always yield fluid, limiting the sensitivity of DL. The results from this study showed that genetic changes can be detected in the absence of morphologic changes in cytologically benign cells, but the application will be limited without a better approach for acquiring cells and a common set of probes for detecting molecular abnormalities that are found in breast malignancies.
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, CA 94143-0808, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Adduci
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Annis
authors.forename: Sandy
authors.initials: S
authors.lastname: DeVries
authors.forename: Karen L
authors.initials: KL
authors.lastname: Chew
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boutin
authors.forename: Gregg
authors.initials: G
authors.lastname: Magrane
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Ljung
authors.forename: Frederic M
authors.initials: FM
authors.lastname: Waldman
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
mesh_terms: D001707:Biopsy, Needle; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D003581:Cytodiagnosis / Q000295:instrumentation / Q000379:methods; D005260:Female; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods; D010641:Phenotype; D015203:Reproducibility of Results