title: Microsatellite changes in nipple aspirate fluid and breast tissue from women with breast carcinoma or its precursors.
abstract: OBJECTIVE
  Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been identified in a variety of human cancers. The purpose of this prospective study was to determine whether (a) DNA can be isolated from nipple aspirate fluid (NAF) and PCR amplified to large fragments, (b) LOH and MSI are detectable in NAF, and (c) LOH and MSI in tissue and NAF increase with disease progression from precursor lesions to cancer.
  
  
  METHODS
  Forty-six matched samples from breast lesions, normal breast, and NAF were microdissected, and DNA was extracted. Eleven microsatellite markers from seven chromosomes that have a high frequency of LOH/MSI in breast cancer were designed and respectively amplified.
  
  
  RESULTS
  LOH and/or MSI were identified in 22 of 46 (48%) breast lesions, including LOH in 8 of 36 (22%) proliferative/papilloma (P/Pap) and 7 of 10 (70%) cancer specimens, whereas MSI was found in 14 of 36 (39%) P/Pap and 6 of 10 (60%) cancer specimens. LOH/MSI loci in which alterations were detected in the 22 tissue specimens were PCR amplified using matched NAF DNA. LOH/MSI was detected in NAF from both P/Pap (5 of 15; 33%) and breast cancer (3 of 7; 43%) samples.
  
  
  CONCLUSIONS
  Our findings suggest that (a) DNA from NAF, a physiological fluid collected noninvasively, can be PCR amplified and used to screen for LOH and MSI alterations that are known to be linked to breast cancer, suggesting that this methodology might prove useful for breast cancer screening, and (b) similar to findings in breast tissue, LOH and MSI alterations increase in frequency with disease progression in NAF, which suggests that NAF is a surrogate for breast tissue which has important prognostic implications.
authors.affiliation: Department of Surgery, Ellis Fischel Cancer Center/University of Missouri, Columbia, Missouri 65212, USA.
authors.forename: Weizhu
authors.initials: W
authors.lastname: Zhu
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.forename: Hormoz
authors.initials: H
authors.lastname: Ehya
authors.forename: John
authors.initials: J
authors.lastname: Lininger
authors.forename: Edward
authors.initials: E
authors.lastname: Sauter
mesh_terms: D014408:Biomarkers, Tumor; D001826:Body Fluids; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D043243:DNA Sequence, Unstable; D018450:Disease Progression; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009558:Nipples / Q000378:metabolism*; D011230:Precancerous Conditions / Q000235:genetics*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA